Dermatology Life Quality Index among Different Cultures: A Neglected Bias Needs to Be Addressed.

Treatment options for leishmaniasis.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

Significance of the pulsed dye laser in treatment of acral infantile hemangioma

Myeloid dendritic cell: From sentinel of immunity to key player of peripheral tolerance?

Myeloid dendritic cells (DC) are "sentinels" of immunity, ideally positioned throughout the body gateways and equipped with unique properties to transport antigens from the periphery to lymphoid tissues. They are professional antigen-presenting cells transmitting incoming infectious signals to T cells, the key players of adaptive immunity. For induction of effective antigen-specific T-cell immunity, crosstalk of DC and naive T cells is mandatory. However, besides this essential immunostimulatory function of DC, consolidated findings from the DC research field in the last 10 years have shown that DC have an additional important function. They act as pivotal players in the peripheral toleranc…

Abstract A004: Systemic RNA vaccines: Connecting effective cancer immunotherapy with antiviral defense mechanisms

Abstract Mechanisms of antiviral host defense are important for survival and evolutionarily optimized for high sensitivity and potency. Intending to harvest the multitude of highly specialized and intertwined pathogen immune defense programs for cancer immunotherapy, we simulated a systemic pathogen intrusion into the blood stream by intravenous injection of lipid-formulated, tumor antigen-encoding mRNA nanoparticles. These RNA-lipoplexes (RNA-LPX) were directed to various lymphoid tissues, including the spleen, lymph nodes and bone marrow, which provide the ideal microenvironment for efficient priming and amplification of T cell responses. Solely the RNA-to-lipid ratio was discovered to de…

Delivering all in one: Antigen-nanocapsule loaded with dual adjuvant yields superadditive effects by DC-directed T cell stimulation

Therapeutic vaccination is and remains a major challenge, particularly in cancer treatment. In this process, the effective activation of dendritic cells by a combination of distinctly acting adjuvants and an antigen is crucial for success. While most common vaccine formulations lack the efficiency to trigger sufficient T cell responses in a therapeutic tumor treatment, nanovaccines offer unique properties to tackle that challenge. Here, we report the stepwise development of a nanocapsule for vaccination approaches, comprising a shell consisting of antigen and loaded with a superadditive adjuvant combination. In a first initial step, we identified the combination of resiquimod (R848) and mur…

LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming.

AbstractA key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function–associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the αL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1–interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely …

Abstract CT034: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent melanoma immunotherapy

Abstract Therapeutic vaccination with tumor antigen-encoding RNAs by local administration is currently being successfully employed in various clinical trials. Advancing from local to more efficient systemic targeting of antigen-presenting cells (APCs), we have developed pioneering RNA-lipoplex (RNA(LIP)) immunotherapeutics for intravenous application based on the employment of well-known lipid carriers without the need for functionalization of particles with molecular ligands. The novel RNA(LIP) formulation has been engineered to preserve RNA integrity after intravenous injection and physicochemically optimized for efficient uptake and expression of the encoded antigen by APCs in various ly…

Differentiation of frontal fibrosing alopecia and Lichen planopilaris on trichoscopy: A comprehensive review.

Trichoscopy in dermatology has opened up the new concept in overcoming the optical challenge faced clinically. It reveals the diagnostic details to the depth of superficial dermis, and thereby increasing the clinician's diagnostic accuracy and the level of confidence. The importance of trichoscopy in cicatricial alopecia is very evident in the current scenario for its precise diagnosis. The clinical picture in delineating lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) from each other and also from other close mimickers such as androgenetic alopecia, alopecia areata, female patterned hair loss, and other cicatricial alopecia is bewildered due to its varied presentation and co…

Dendritic cell activation by combined exposure to anti-CD40 plus interleukin (IL)-12 and IL-18 efficiently stimulates anti-tumor immunity

Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (T(H)1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce T(H)1 immunity [anti-CD40, interleukin (IL)-12, IL-18], with the aim to trigger a T(H)1 driven anti-tumor CTL response. When compared with untreated DC or DC treated with anti-CD40 alone, DC matured with anti-CD40 plus IL-12 and IL-18 expressed significantly more IFN-gamma and IL-12, induced enhanced CD8(+…

Antigen dose-dependent suppression of murine IgE responses is mediated by CD4−CD8− double-negative T cells

Background The IgE response against protein antigens is profoundly influenced by the dose used for sensitization. Objective The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation. Methods Wild-type mice as well as T helper (Th)1-deficient IL-12p40(-/-) and IFN-gamma(-/-) mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets …

Differential gene expression analysis identifies murine Cacnb3 as strongly upregulated in distinct dendritic cell populations upon stimulation

Langerhans cells (LCs) represent the dendritic cell (DC) population in the epidermis. Among the set of genes induced in primary mouse LCs in response to stimulation, both isoforms of the voltage-dependent Ca²(+) channel (VDCC) regulatory subunit Cacnb3 as well as the DC maturation marker Fscn1 were upregulated most strongly. Comparable results were obtained for a recently described myeloid DC line (SP37A3). Other antigen presenting cell populations, namely, bone marrow-derived DCs, macrophages and primary B cells, showed no stimulation-associated upregulation of Cacnb3 expression. Pharmacological inhibition of Ca²(+) channel activity during the stimulation of SP37A3 cells enhanced their T c…

A Brief Synopsis on Scalp Melanoma

Melanoma constitutes one of the most sinister and troublesome malignancies encountered by humanity. Generally, the diagnosis of advanced melanoma connotes a grave prognosis, prompting a sense of looming threat of death, however, the early-stage detected disease responds well to robust treatment resulting in reasonable survivorship. Scalp melanomas are even more troublesome, because they typically exhibit more aggressive biologic behavior and are often diagnosed at a late stage. This review tries to comprehensively highlight the various diagnostic, therapeutic, and outcome aspects of scalp melanomas. The literature research includes peer-reviewed articles (clinical trials or scientific revie…

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 1: Epidemiology, Genetics and Diagnosis

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

A novel plasmid DNA electroporation method allows transfection of murine DC.

Under steady state conditions dendritic cells (DC) exert tolerogenic function, but acquire potent immunogenic function due to strong upregulation of costimulatory molecules and proinflammatory cytokines. In numerous studies the potential of modified DC to induce tolerance or immune reactions towards a distinct antigen has been demonstrated. However, DC are refractory to transfection with plasmid DNA by non-viral methods. In this study we have tested the suitability of a newly developed electroporation device to transfect immature murine bone-marrow derived DC (BM-DC). Transfected BM-DC expressed reporter molecules at considerable extent which renders this method suitable to perform all kind…

Effect of estrogen in malignant melanoma

Background Melanoma is associated with poor prognosis in its advanced stages. Potential influence of estrogen and its metabolites on melanoma growth has been suggested. Aims The objective of this review was to provide an overview on the evidence related to estrogen in malignant melanoma. Materials and methods Literature search using PubMed, Google Scholar and relevant cross-references of the retrieved articles was performed to review relevant published articles related to estrogen and its effects in malignant melanoma. Results Effect of estrogen signaling on a tissue largely depends on the relative expression of estrogen receptors (ER) α and β. Gender differences in melanoma may be explaine…

Two brothers with confluent and reticulated papillomatosis.

Long-lasting tumor response on short-time administration of vemurafenib—A case report

Vemurafenib has been approved since 2011 in the United States for the treatment of advanced BRAF V600–mutated melanoma as first-line therapy. Although it significantly prolongs overall and progression-free survival, most patients relapse within 6 to 8 months owing to acquisition of drug resistance. New findings suggest that discontinuous dose administration of vemurafenib might prolong response to vemurafenib, but it is unclear whether modified cell signalling or other mechanisms, such as immune-mediated effects, are responsible for this effect.

Acquired symmetric asymptomatic lesions at the inner corners of the eyes

Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T cells, and favors expansion of regulatory T cells

AbstractRetroviruses have developed immunmodulatory mechanisms to avoid being attacked by the immune system. The mechanisms of this retrovirus-associated immune suppression are far from clarified. Dendritic cells (DCs) have been attributed a decisive role in these pathogenic processes. We have used the Friend retrovirus (FV) mouse model in order to acquire further knowledge about the role of infection of DCs in virus-induced immunosuppression. About 20% of the myeloid DCs that were generated from the bone marrow of FV-infected mice carried FV proteins. The infection was productive, and infected DCs transmitted the virus in cell culture and in vivo. FV infection of DCs led to a defect in DC …

Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity

Background IL-10–treated dendritic cells (DCs) have been shown to inhibit T-cell responses through induction of anergy and regulatory T cells in various model systems, including allergic inflammation, but the factors being involved in this inhibition are still unclear. Objective This study set out to analyze such factors produced or induced by IL-10–treated DCs by using gene expression profiling and to explore their function. Methods CD4 + T cells from allergic donors were stimulated with autologous monocyte-derived allergen-pulsed mature DCs or IL-10–treated DCs. After 24 hours, the transcriptional profile was analyzed by using Affymetrix technology. Results were validated by using quantit…

Interleukin 23p19 inhibitors in chronic plaque psoriasis with focus on mirikizumab: A narrative review.

Psoriasis, a T-cell mediated chronic dermatosis, has a complex etiopathogenesis. There has been extensive research into the aberrant immune response, which leads to the formation of clinical lesions, and the need for developing better and safer drugs has been unrelenting. The past two decades of research has opened up new areas of the immune pathway that can be targeted in order to control the disease. Therefore, we have seen the emergence of biologics which either target T-cell receptors or inhibit Tumor Necrosis Factor-alpha (TNF-α) or inhibit interleukins (IL) like IL-12, IL-17, IL-17 receptor, and more recently IL-23. Drugs specifically targeting the p19 subunit of IL-23 have shown prom…

The RNA binding protein tristetraprolin influences the activation state of murine dendritic cells

Abstract Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state conditions. Upon triggering by activation signals they initiate strong immune responses. The activation of DCs is accompanied by a rapid upregulation of proinflammatory cytokines, which were shown in other cell types to be regulated by mechanisms at the transcriptional and posttranscriptional level. Tristetraprolin (TTP), an important RNA binding protein, is involved in the regulation of mRNA stability of such cytokines. In this study we analyzed the significance of TTP for mouse DCs, which were derived from TTP −/− and WT bone marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP −/− mice expres…

Hämatom, Serom oder solider Tumor – Fallstricke in der Sonografie

Screening for distress in routine oncological care-a survey in 520 melanoma patients.

Introduction Despite the increasing incidence of melanoma little is known about patients' emotional distress associated with this disease. Supplemented by the problem list (PL), the distress thermometer (DT) is a recommended screening instrument to measure psychosocial distress in cancer patients. Our objective was to explore the acceptance and the feasibility of the DT and PL as a concise screening tool in an ambulatory setting for routine care and to elucidate determinants of distress in melanoma patients with regard to sociodemographic and clinical variables. Methods Consecutive melanoma outpatients were asked to complete the DT with the PL prior to their scheduled consultation. Demograp…

Brief S2k guidelines - Merkel cell carcinoma

Jurgen C. Becker, Chalid Assaf, Dirk Vordermark, Sven N. Reske, Jorg Hense, Therese Dettenborn, Oliver Seitz, Stephan Grabbe (1) Division of General Dermatology, Graz University Hospital, Austria (2) Department of Dermatology, HELIOS Klinikum, Krefeld, Germany (3) Department of Radiotherapy, University Hospital Halle (Saale), Germany (4) Department of Nuclear Medicine, University Hospital Ulm, Germany (5) Department of Internal Medicine, University Hospital Essen, Germany (6) Department of Plastic Surgery, Hornheide Clinic, Munster, Germany (7) Department of Oral and Maxillofacial Surgery, University of Frankfurt Hospital, Germany (8) Department of Dermatology, Mainz University Hospital, Ge…

Abstract CT202: IVAC MUTANOME: Individualized vaccines for the treatment of cancer

Abstract Cancer arises from the accumulation of genomic alterations and epigenetic changes that constitute a hallmark of cancer. Owing to the molecular heterogeneity in cancer, only a minor fraction of patients profit from approved therapies. Available targeted therapies can only address alterations common to a particular type of cancer and induce transient effects due to the generation of resistant sub-clones. In contrast, the IVAC MUTANOME project aims to immunologically target multiple cancer mutations uniquely expressed in a given patient's tumor. The IVAC MUTANOME approach should be applicable to the majority of patients irrespective of the tumor entity and offers the potential to expl…

Mutated cylindromatosis gene affects the functional state of dendritic cells

Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling. Here, we report that DC derived from transgenic mice, which solely express a naturally occurring CYLD isoform (CYLD(ex7/8)), display a higher content of nuclear RelB and express elevated levels of NF-κB family members as well as of known NF-κB-target genes comprising costimulatory molecules and pro-inflammatory cytokines, as compared with WT DC. Accordingly, unstimulated CYLD(ex7/8) DC exhibited a significantly higher primary allogenic T-cell stimulatory capacity than WT DC and exerted no tolerogenic activity. Tr…

A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in vivo.

Dendritic cells (DCs) constitute an attractive target for specific delivery of nanovaccines for immunotherapeutic applications. Here we tested nano-sized dextran (DEX) particles to serve as a DC-addressing nanocarrier platform. Non-functionalized DEX particles had no immunomodulatory effect on bone marrow (BM)-derived murine DCs in vitro. However, when adsorbed with ovalbumine (OVA), DEX particles were efficiently engulfed by BM-DCs in a mannose receptor-dependent manner. A DEX-based nanovaccine containing OVA and lipopolysaccharide (LPS) as a DC stimulus induced strong OVA peptide-specific CD4(+) and CD8(+) T cell proliferation both in vitro and upon systemic application in mice, as well a…

Prurigo nodularis as index symptom of (non-Hodgkin) lymphoma: ultrasound as a helpful diagnostic tool in dermatological disorders of unknown origin

Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synergy.

Abstract Synergistic activation of dendritic cells by combinations of TLR ligands requires both MyD88- and TRIF-dependent signaling. Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the …

Pembrolizumab-induzierter Lichen planus pemphigoides bei einem Patienten mit metastasiertem Melanom

Increased risk of angiosarcoma secondary to cancer radiotherapy: Case series and review of the treatment options.

Angiosarcomas (ASs) are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy or chronic lymphedema. With only 1-5% of all sarcomas, the incidence seems low, but for the affected patient due to the extremely poor prognosis and the limited treatment options, the fate is often inevitable. Radiotherapy, chemotherapy, or "target therapy" have been used in the management of AS, but represent individual case decisions without lasting evidence. Over the past few years, breast-conserving surgery followed by radiation therapy, known as breast-conserving therapy (BCT), is being employed as a standard treatment for early-stage breast cancer,…

Role of Hypoxia and the Adenosine System in Immune Evasion and Prognosis of Patients with Brain Metastases of Melanoma: A Multiplex Whole Slide Immunofluorescence Study

Simple Summary The introduction of immune-checkpoint inhibitors improved the therapeutic landscape for patients with advanced malignant melanoma. However, many patients, including patients with melanoma brain metastases, do not derive benefit from immune-checkpoint blockade. Hence, biomarkers are needed to identify potential mechanisms of resistance and optimize patient selection. This study aimed to explore the role of hypoxia-mediated immunosuppression within the tumor microenvironment of patients with metastatic melanoma using multiplex immunofluorescence. We analyzed the prognostic relevance of the hypoxia surrogate marker GLUT-1, the adenosine-synthesizing ectoenzymes CD73/CD39, and th…

Achieving dendritic cell subset-specific targeting in vivo by site-directed conjugation of targeting antibodies to nanocarriers

AbstractThe major challenge of nanocarrier-based anti-cancer vaccination approaches is the targeted delivery of antigens and immunostimulatory agents to cells of interest, such as specific subtypes of dendritic cells (DCs), in order to induce robust antigen-specific anti-tumor responses. An undirected cell and body distribution of nanocarriers can lead to unwanted delivery to other immune cell types like macrophages reducing the vaccine efficacy. An often-used approach to overcome this issue is the surface functionalization of nanocarriers with targeting moieties, such as antibodies, mediating cell type-specific interaction. Numerous studies could successfully prove the targeting efficiency…

Systemische Immunsuppression in Zeiten von COVID‐19: Müssen wir umdenken?

Zusammenfassung Die aktuelle SARS‐CoV‐2 Pandemie gefährdet vor allem ältere Menschen mit kardiopulmonalen und metabolischen Vorerkrankungen. In aktueller Diskussion ist jedoch auch, ob Patienten unter immunsuppressiver Therapie ebenfalls ein höheres Risiko haben, im Fall einer COVID‐19‐Erkrankung einen schweren Krankheitsverlauf zu erleiden. Grundsätzlich gibt es derzeit jedoch keine Datenlage für eine generelle Reduktion oder Pausierung einer Immunsuppression bei Patienten mit Autoimmunerkrankungen in Zeiten der SARS‐CoV‐2‐Pandemie. Da es jedoch derzeit weder eine wirksame Therapie, noch einen entsprechenden Impfschutz gibt, sollten wir uns gezielt mit der Problematik chronisch‐immunsuppri…

Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells.

Advanced glycation endproducts (AGEs) of food proteins resulting from the Maillard reaction after cooking or heating may have particular importance in food allergy. The underlying immunological mechanisms are only poorly understood. The aim of the study was to examine the effects of AGE derived from the model food allergen ovalbumin (AGE-OVA) on dendritic cells (DCs), their immunostimulatory capacity and the T-cell response compared with regular OVA. For this purpose, human immature DCs were exposed to fluorescein isothiocyanate (FITC)-labelled AGE-OVA and FITC-labelled regular OVA and uptake was analysed by flow cytometry and fluorescence microscopy. Furthermore, autologous CD4(+) T-cell p…

Therapeutic options in vitiligo with special emphasis on immunomodulators: A comprehensive update with review of literature

Vitiligo is a relatively common disorder characterized by areas of depigmented skin. It may be associated with social stigma and adversely affects the quality of life. Although many treatment options are available, none is curable. The search continues for an effective therapeutic option. New targeted options include biologics and other immunomodulatory agents, with varying degrees of evidence. We have discussed briefly the therapeutic options with special emphasis on the newer immunomodulatory agents. We undertook a comprehensive English literature search across multiple databases such as PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords (alone and in combination) and MeSH items…

Update in minimally invasive periorbital rejuvenation with a focus on platelet-rich plasma: A narrative review.

Background The periorbital region is among the first areas to be affected by the process of aging, which is influenced by genetic and constitutional factors. As the region plays an important role in overall facial appearance, rejuvenation of the area has immense cosmetic benefit and various treatment modalities have been used to achieve the same. Aims This article reviews commonly used non-surgical and minimally invasive modalities for periorbital rejuvenation. Methods The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles.…

Safety of the current drug treatments for vitiligo

Introduction: Vitiligo is an acquired depigmenting skin disorder adversely affecting the patient's quality of life. Despite the presence of several treatment modalities, ranging from medical to physical to surgical options, none is curative. Each modality has its own drawbacks and side effects. Thus, the treatment modality needs to be tailored for each individual patient taking into consideration the disease characteristics and also its efficacy and safety to obtain a favorable risk-benefit ratio.Areas covered: This review highlights the different treatment modalities utilized in vitiligo up until 4 November 2019 along with their adverse effects and contraindications, if any.Expert opinion:…

Protein corona–mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses

Background Nanoparticle (NP)–based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and their effect on the functional properties of NPs is poorly understood. Objectives We analyzed the relevance of the protein corona on cell type–selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy. Methods The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DE…

Updated review on prognostic factors in mycosis fungoides and new skin lymphoma trials

BACKGROUND Ten-year survival rates in mycosis fungoides (MF) broadly varies, however, there is no standardized prognostic index available. This is presumably due to low prevalence, heterogeneity, and diagnostic challenges in MF. Recent studies have focused on identifying objective prognostic indices by using different parameters for survival determinants. The Cutaneous Lymphoma International Prognostic Index (CLIPI) and the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) represent prototypical studies that identify prognostic factors, seeking to improve management and outcomes in early-stage MF. Detecting these factors and stratifying MF patients according to their …

Grüntee‐Extrakt als erfolgreiche topische Behandlungsoption bei Kindern mit Condylomata acuminata im Perianalbereich

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – update 2018

Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical exc…

Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells

Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…

Green tea extract as a successful topical treatment option in children with perianal condylomata

Toll like receptor mediated immune stimulation can be visualized in vivo by [ 18 F]FDG-PET

Abstract Introduction High uptake of [ 18 F]-2-fluorodeoxyglucose ([ 18 F]FDG) by inflammatory cells is a frequent cause of false positive results in [ 18 F]FDG-positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [ 18 F]FDG-PET after stimulation with TLR ligands and specific antibodies. Methods In vivo [ 18 F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with Cp…

Non‐invasive diagnostic techniques in pigmentary skin disorders and skin cancer

Background Diagnosis of pigmentary skin disorders, pre-cancerous and cancerous skin diseases is traditionally relied on visual assessment. The most widely applied invasive diagnostic technique is the skin biopsy. There have been significant technological advances in non-invasive diagnostic methods for skin disorders. Objective The objective of this article is to discuss different non-invasive diagnostic modalities, used in the diagnosis of pigmentary skin disorders and cutaneous cancers. Methods Comprehensive literature search was performed to screen articles related to non-invasive diagnostic techniques in pigmentary skin disorders and cutaneous cancers. Articles published in journals inde…

Granulomatous mycosis fungoides, a rare subtype of cutaneous T-cell lymphoma

Granulomatous mycosis fungoides (GMF) is an unusual histologic subtype of cutaneous T-cell lymphoma.1 The diagnosis of GMF is usually established after observation of a granulomatous inflammatory reaction associated with a malignant lymphoid infiltrate. Epidermotropism, a clue to diagnosis in classical mycosis fungoides (MF) may be absent in about 47% of cases of GMF.2 In some instances, the granulomatous component may be intense and obscures the lymphomatous component of the infiltrate.1 There are no distinctive clinical patterns associated with GMF.1, 3

A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for potent melanoma immunotherapy

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

Nanocarriers (NC) are very promising tools for cancer immunotherapy. Whereas conventional vaccines are based on the administration of an antigen and an adjuvant in an independent fashion, nanovaccines can facilitate cell-specific co-delivery of antigen and adjuvant. Furthermore, nanovaccines can be decorated on their surface with molecules that facilitate target-specific antigen delivery to certain antigen-presenting cell types or tumor cells. However, the target cell-specific uptake of nanovaccines is highly dependent on the modifications of the nanocarrier itself. One of these is the formation of a protein corona around NC after in vivo administration, which may potently affect cell-speci…

IL-10 Controls Ultraviolet-Induced Carcinogenesis in Mice

Abstract UV radiation-induced immunosuppression contributes significantly to the development of UV-induced skin cancer by inhibiting protective immune responses. IL-10 has been shown to be a key mediator of UV-induced immunosuppression. To investigate the role of IL-10 during photocarcinogenesis, groups of IL-10+/+, IL-10+/−, and IL-10−/− mice were chronically irradiated with UV. IL-10+/+ and IL-10+/− mice developed skin cancer to similar extents, whereas IL-10−/− mice were protected against the induction of skin malignancies by UV. Because UV is able to induce regulatory T cells, which play a role in the suppression of protective immunity, UV-induced regulatory T cell function was analyzed…

Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic melanoma

PeptoSomes for Vaccination: Combining Antigen and Adjuvant in Polypept(o)ide-Based Polymersomes.

In this work, the first vaccine is reported based on a PeptoSome, which contains a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide-based polymersomes built of a block-copolymer with polysarcosine (PSar) as the hydrophilic block (X n = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the hydrophobic one (X n = 46). The polypept(o)ide is obtained with low dispersity index of 1.32 by controlled ring-opening polymerization. Vesicle formation by dual centrifugation technique allows for loading of vesicles up to 40 mol%. PeptoSomes are characterized by multiangle dynamic light scattering, static light scattering, and cryogenic transmission electron microscopy (cryoTEM…

Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis.

Allergic contact dermatitis (ACD) is one of the most common skin diseases, consisting of sensitization and elicitation phases. With the advancement of technology and the discovery of new types of immune cells, our knowledge of the immunological mechanisms of contact hypersensitivity (CHS) as a murine model of ACD has expanded significantly in the past decade. For example, by introducing regulatory T cells, CD4(+) T-helper 17 cells, and Langerin-positive dermal dendritic cells, the initiation and termination mechanism of CHS has been revealed. In addition, the role of mast cells in CHS, long a matter of debate, has become apparent by developing conditional mast cell-deficient mice. Moreover,…

ADF Winter School-An exciting concept of the Arbeitsgemeinschaft Dermatologische Forschung to connect young scientists and clinician scientists in Dermatology at the top of Germany

Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients’ and doctors’ views

Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2 μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were rou…

Can SARS‐CoV‐2 vaccine increase the risk of reactivation of Varicella zoster? A systematic review

Abstract Introduction Although the COVID‐19 vaccination is deemed safe, exact incidence and nature if adverse effects, particularly dermatological ones, are still unknown. Objective To describe the demographic, clinical, morphological characteristics, outcomes, and timing of development of herpes zoster to the various COVID‐19 vaccines. And to identify on whether COVID‐19 vaccine has temporal relationship between development of herpes zoster (HZ). Methods We have performed a systemic review of articles from PubMed and Embase using MeSH and keywords like “Shingles,” “Herpes zoster,” “Varicella zoster,” “COVID‐19,” “Vaccine,” “SARS‐CoV‐2.” No filters including country of publication, language…

Regulatory T Cells Prevent Neutrophilic Infiltration of Skin during Contact Hypersensitivity Reactions by Strengthening the Endothelial Barrier

The healing phase of contact hypersensitivity reactions is critically dependent on regulatory T cells (Tregs), but even the early inflammatory phase, that is, 6-24 hours after induction of a contact hypersensitivity reaction, is susceptible to Treg-mediated suppression. To investigate the underlying mechanisms, we injected Tregs before the challenge and analyzed the skin-infiltrating cells as early as 6 hours later. Early on, we found mainly neutrophils in the challenged skin, but only a few T cells. This influx of neutrophils was blocked by the injection of Tregs, indicating that they were able to prevent the first wave of leukocytes, which are responsible for starting an immune reaction. …

Sentinel lymph node biopsy in malignant melanoma of the head and neck

Abstract Background The aim of this retrospective study was to investigate sentinel lymph node biopsy in patients with head and neck melanoma. Materials and methods Patients who underwent SLNB between 2010 and 2016 were comprised. Epidemiological, radiological, and surgical data were collected and compared to histological findings. Patients who underwent primary complete lymph node dissection were excluded. Results 74 patients underwent SLNB during this period. The most common tumor localizations were the cheek (20.4%) and ears (20.4%). Overall, 256 sentinel lymph nodes (SLN) were detected and removed, most frequently in Robbins-levels IIA and IIB as well as in the surrounding of the paroti…

Clinical efficacy of blue light full body irradiation as treatment option for severe atopic dermatitis.

Background Therapy of atopic dermatitis (AD) relies on immunosuppression and/or UV irradiation. Here, we assessed clinical efficacy and histopathological alterations induced by blue light-treatment of AD within an observational, non-interventional study. Methodology/Principal Findings 36 patients with severe, chronic AD resisting long term disease control with local corticosteroids were included. Treatment consisted of one cycle of 5 consecutive blue light-irradiations (28.9 J/cm2). Patients were instructed to ask for treatment upon disease exacerbation despite interval therapy with topical corticosteroids. The majority of patients noted first improvements after 2–3 cycles. The EASI score w…

5‐Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety

Androgenetic alopecia (AGA) is a multifactorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5-alpha reductase (5-AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5-alpha reductase inhibitor (5-ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning ferti…

β2Integrin deficiency yields unconventional double-negative T cells distinct from mature classical natural killer T cells in mice

Expressed on leucocytes, beta(2) integrins (CD11/CD18) are specifically involved in leucocyte function. Using a CD18-deficient (CD18(-/-)) mouse model, we here report on their physiological role in lymphocyte differentiation and trafficking. CD18(-/-) mice present with a defect in the distribution of lymphocytes with highly reduced numbers of naïve B and T lymphocytes in inguinal and axillary lymph nodes. In contrast, cervical lymph nodes were fourfold enlarged harbouring unconventional T-cell receptor-alphabeta (TCR-alphabeta) and TCR-gammadelta CD3(+) CD4(-) CD8(-) (double-negative; DN) T cells that expanded in situ. Using adoptive transfer experiments, we found that these cells did not h…

Targeting cells of the immune system: mannosylated HPMA–LMA block-copolymer micelles for targeting of dendritic cells

Background: Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy. Materials & methods: Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP. Both types of copolymers wer…

Prävention im Alter durch Risikovermeidung, Früherkennung und frühe Behandlung

Der wichtigste Risikofaktor fur Brustkrebs ist bei Frauen und Mannern das Alter. Brustkrebs beim Mann ist selten; Untersuchungen zur Fruherkennung werden deshalb nicht empfohlen; diese sind nur bei Veranderungen oder Beschwerden erforderlich (S3-Leitlinie Diagnostik 2018). Fur Frauen liegt das Lebenszeitrisiko fur Brustkrebs bei 12,8 %, d. h. dass jede achte Frau im Verlauf ihres Lebens an Brustkrebs erkrankt. Selten tritt Brustkrebs bei Frauen unter 30 Jahren auf. Der groste Teil der Frauen erkrankt zwischen dem 50. und 70. Lebensjahr; Mitte 60 ist das Risiko am hochsten. Etwa 37 % erkranken nach dem 70. Lebensjahr; Brustkrebs kann jedoch noch bis ins hohe Alter von 90 Jahren und mehr auft…

Platelet-Derived GARP Induces Peripheral Regulatory T Cells—Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis

Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet&ndash

Serum S100B levels correlate with clinical benefit in a metastatic melanoma patient treated by CTLA-4 blockade: a case report.

<b><i>Background:</i></b> Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells. In patients with metastatic melanoma, anti-CTLA-4 antibody therapy with ipilimumab achieves durable cancer regression in approximately 10-15% of patients. In the face of complex and sometimes delayed tumor response patterns, prognostic and predictive biomarkers are needed to monitor therapy outcomes and to identify early potential long-term survivors who might also benefit from therapy re-induction. <b><i>Case Report:</i></b> The clinical case of a 49-year-old male patient with metastatic melanoma and u…

Sodium chloride is an ionic checkpoint for human TH2 cells and shapes the atopic skin microenvironment.

The incidence of allergic diseases has increased over the past 50 years, likely due to environmental factors. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation characteristic of atopic diseases remain unclear. It has previously been reported that dietary sodium chloride promotes the polarization of T helper 17 (T(H)17) cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes T(H)2 cell responses on multiple regulatory levels. Sodium chloride enhanced interleukin-4 (IL-4) and IL-13 production while suppressing interferon-gamma (IFN-gamma) production i…

Platelet-neutrophil aggregates promote skin pathology in psoriasis

AbstractPsoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of n…

Discontinuation of braf/mek-directed targeted therapy after complete remission of metastatic melanoma : a retrospective multicenter adoreg study

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-res…

A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma.

3136 Background: Cancer vaccines are considered unsuitable for patients with advanced tumours and have not been clinically successful. Methods: Lipo-MERIT is an ongoing phase 1/2 trial (NCT02410733) with melanoma FixVac, a liposomal RNA vaccine targeting four non-mutant shared tumour-associated antigens (TAAs) (MAGE-A3, NY-ESO-1, tyrosinase, TPTE). Patients with stage IIIB-C and IV melanoma are eligible. The trial comprises 7 dose escalation and 3 dose expansion cohorts, the latter with FixVac alone or combined with anti-PD1. Eight doses of FixVac are administered i.v. weekly/bi-weekly followed by optional continued monthly treatment. This abstract summarizes the findings of an exploratory…

CD40-Activated B Cells Migrate Towards Secondary Lymphoid Organs And Interact Dynamically With T Cells

IVAC MUTANOME: A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma

Complications of botulinum toxin and fillers: A narrative review

Background Cosmetic surgery and esthetic procedures have become a billion dollar industry owing to the ever-growing demand of the population to stay young. The injectable treatments including fillers and botulinum toxin have become highly popular because of their quick, predictable and lasting results in the management of facial wrinkles and rejuvenation. Although these treatment modalities are relatively safe, they are associated with certain side effects. Aims In this review, we will focus on the complications of fillers and botulinum toxin. Patients/methods The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by se…

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

Review of biologics in allergic contact dermatitis

The resistant and recalcitrant nature of severe allergic contact dermatitis (ACD) makes its management challenging. With advances in the understanding of the cellular and molecular pathogenesis of ACD, newer therapeutic targets are becoming apparent. In particular, the use of biologics has gained momentum, given the specificity of their action. This article aims to review the presently available data on the use of biologics in ACD. English-language-based literature available on the use of biological therapy was thoroughly probed in the following databases as on October 14, 2019: PubMed, Google Scholar, The Cochrane library, Embase, Scopus, and EBSCO. The following keywords were used: "conta…

Density of conjugated antibody determines the extent of Fc receptor dependent capture of nanoparticles by liver sinusoidal endothelial cells

Despite considerable progress in the design of multifunctionalized nanoparticles (NPs) that selectively target specific cell types, their systemic application often results in unwanted liver accumulation. The exact mechanisms for this general observation are still unclear. Here we asked whether the number of cell-targeting antibodies per NP determines the extent of NP liver accumulation and also addressed the mechanisms by which antibody-coated NPs are retained in the liver. We used polysarcosine-based peptobrushes (PBs), which in an unmodified form remain in the circulation for >24 h due to the absence of a protein corona formation and low unspecific cell binding, and conjugated them with …

Factors accelerating recurrences and secondary tumors in cutaneous squamous cell carcinoma

To investigate factors that affect and also decrease the duration for recurrences and secondary tumors in cSCC. A retrospective study was conducted for all patients who were treated for a cSCC of the head and neck between 2009 and 2016. Anamnestic as well as epidemiological and histological data were noted and correlated with the occurrence of recurrences and secondary cancers. The duration between surgery and these events was used to determine if histological factors accelerate their occurrence. The highest risk for recurrences was seen in patients with previous skin cancers (RR 3.23). Histological ulceration (p = 0.003) and grading (p = 0.031) of the tumor were found as significant factor…

CD11b Regulates Fungal Outgrowth but Not Neutrophil Recruitment in a Mouse Model of Invasive Pulmonary Aspergillosis

Abstract Background and Aims: In immunosuppressed individuals Aspergillus (A.) fumigatus is a frequent cause of invasive pulmonary aspergillosis (IPA) which is highly associated with relevant morbidity and mortality. Moreover, it often occurs in patients suffering from leukocyte-adhesion deficiency type 1 (LAD1) which is triggered by a functional loss of CD18 in ß2 integrin receptors as these receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit. ß2 integrin receptors are differentially expressed by leukocytes, and are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Here, we asked …

Zwei Brüder mit Papillomatosis confluens et reticularis.

Abstract CT156: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for immunotherapy of malignant melanoma

Abstract Therapeutic vaccination with tumor antigen-encoding RNAs is being investigated in various clinical trials. Typically, the RNA vaccine is administered intradermally, subcutaneously or intranodally with the intention to get expression of the encoded antigens in local antigen-presenting cells (APCs). We have developed a novel class of RNA-lipoplex (RNA(LIP)) immunotherapeutics for intravenous application, which allow systemic targeting of APCs. RNA(LIP) is a novel nanoparticulate formulation of lipid-complexed mRNA which selectively delivers the functional mRNA to APCs in lymphoid compartments body-wide for efficient mRNA uptake and expression of the encoded antigen by APCs. Moreover,…

Vaccination with trifunctional nanoparticles that address CD8+ dendritic cells inhibits growth of established melanoma

Aim: We wanted to assess the potency of a trifunctional nanoparticle (NP) that targeted and activated CD8+ dendritic cells (DC) and delivered an antigen to induce antitumor responses. Materials & methods: The DC targeting and activating properties of ferrous NPs conjugated with immunostimulatory CpG-oligonucleotides, anti-DEC205 antibody and ovalbumin (OVA) as a model antigen to induce antigen-specific T-cell responses and antitumor responses were analyzed. Results: OVA-loaded NP conjugated with immunostimulatory CpG-oligonucleotides and anti-DEC205 antibody efficiently targeted and activated CD8+ DC in vivo, and induced strong OVA-specific T-cell activation. Vaccination of B16/OVA tum…

The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

Simple Summary Immunotherapy improved the therapeutic landscape for patients with advanced cancer diseases. However, many patients do not benefit from immunotherapy. The bidirectional crosstalk between myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) contributes to immune evasion, limiting the success of immunotherapy by checkpoint inhibitors. This review aims to outline the current knowledge of the role and the immunosuppressive properties of MDSC and Treg within the tumor microenvironment (TME). Furthermore, we will discuss the importance of the functional crosstalk between MDSC and Treg for immunosuppression, issuing particularly the role of cell adhesion molecules. …

Multifaceted contributions of epidermal langerhans cells to cutaneous carcinogenesis.

Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAH) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LC) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LC rapidly internalize an…

Abstract CT022: IVAC® MUTANOME - A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma

Abstract One of the hallmarks of cancer is the inherent instability of the genome leading to multiple genomic alterations and epigenetic changes that ultimately drive carcinogenesis. These processes lead to a unique molecular profile of every given tumor and to substantial intratumoral heterogeneity of cancer tissues. Recently, a series of independent reports revealed that pre-formed neoantigen specific T-cell responses are of crucial relevance for the clinical efficacy of immune checkpoint inhibitors. However, spontaneous immune recognition of neoantigens seems to be a rare event with only less than 1% of mutations inducing a T-cell response in the tumor-bearing patient. Accordingly, only …

549 An RNA-lipoplex (RNA-LPX) vaccine demonstrates strong immunogenicity and promising clinical activity in a Phase I trial in cutaneous melanoma patients with no evidence of disease at trial inclusion

BackgroundLipo-MERIT is an ongoing, first-in-human, open-label, dose-escalation Phase I trial investigating safety, tolerability and immunogenicity of BNT111 in patients with advanced melanoma. BNT111 is an RNA-LPX vaccine targeting the melanoma tumor-associated antigens (TAAs) New York esophageal squamous cell carcinoma 1 (NY-ESO-1), tyrosinase, melanoma-associated antigen 3 (MAGE-A3), and transmembrane phosphatase with tensin homology (TPTE). A previous exploratory interim analysis showed that BNT111, alone or combined with immune checkpoint inhibition (CPI), has a favorable adverse event (AE) profile, gives rise to antigen-specific T-cell responses and induces durable objective responses…

Systemic immunosuppression in times of COVID‐19: Do we need to rethink our standards?

Summary The current SARS‐CoV‐2 pandemic particularly endangers older people with pre‐existing cardiopulmonary and metabolic conditions. However, it is also currently under discussion whether patients under immunosuppressive therapy also have a higher risk of suffering a severe course of the COVID‐19 disease. In principle though, there is currently no data available for a general reduction or pause of immunosuppression in patients with autoimmune diseases because of the SARS‐CoV‐2 pandemic. However, since there is currently neither an effective therapy nor corresponding vaccination protection, the indication for a prolonged immunosuppressive therapy should be made with special care. In parti…

Synthesis of the Data on COVID-19 Skin Manifestations: Underlying Mechanisms and Potential Outcomes

Abstract The incidence of coronavirus disease 2019 (COVID-19)-related skin manifestations has progressively grown, in parallel with the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. The available evidence indicates that cutaneous signs are heterogeneous and can be divided as follows: a) erythematous rashes, b) lesions of vascular origin, c) vesicular rashes, d) urticarial rashes, and e) acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM) and other polymorphic/atypical reactions. Most cutaneous manifestations appear simultaneously or after respiratory and/or systemic symptoms such as fever, even if rarely urticaria has been reported as…

Dendritic cells lentivirally engineered to overexpress interleukin-10 inhibit contact hypersensitivity responses, despite their partial activation induced by transduction-associated physical stress.

Background Dendritic cells (DCs) constitute an attractive target for immunotherapeutic approaches. Because DCs are largely refractory to transfection with plasmid DNA, several viral transduction protocols were established. The potential side-effects of lentiviral transduction on the phenotype and activation state of DCs left unstimulated after transduction have not been assessed. There is a need to analyse these parameters as a result of the requirement of using DCs with a low activation state for therapeutic strategies intended to induce tolerance. Methods Lentivirally-transduced bone marrow (BM)-derived DCs (LV-DCs) in comparison with mock-transduced (Mock-DCs) and untreated DCs were anal…

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit p…

Combination therapy of recalcitrant severe psoriasis with psoriatic arthritis, diabetes nephropathy, and liver cirrhosis

Objective Treatment of recalcitrant moderate-to-severe psoriasis can be challenging. Combination therapy of biologics and immunosuppressive agents can be a new strategy for treating therapy-resistant cases with comorbidities, where many systemic medications are contraindicated. Case presentation We report a case of a 62-year-old diabetic man with a 30-year history of severe plaque psoriasis and psoriatic arthritis with cirrhosis and diabetic nephropathy that was treated successfully in combination with apremilast and etanercept after multiple previous unsuccessful treatment attempts. Conclusion There are no data supporting the combination of apremilast and etanercept in the management of re…

Anticoagulation with Factor Xa Inhibitors Is Associated with Improved Overall Response and Progression-Free Survival in Patients with Metastatic Malignant Melanoma Receiving Immune Checkpoint Inhibitors—A Retrospective, Real-World Cohort Study

Immune checkpoint inhibitors (ICI) significantly improved the prognosis of advanced melanoma patients. However, many patients do not derive long-term benefit from ICI therapy due to primary and acquired resistance. In this regard, it has been shown that coagulation factors contribute to cancer immune evasion and might therefore promote resistance to ICI. In particular, recent observations in murine systems demonstrated that myeloid-derived factor Xa (FXa) impedes anti-tumor immunity in the tumor microenvironment and that the oral FXa inhibitor (FXa-i) rivaroxaban synergizes with ICI. The synergistic effect of FXa inhibitors with clinical ICI therapy is unknown. We performed a retrospective …

LAight® Therapy Significantly Enhances Treatment Efficacy of 16 Weeks of Topical Clindamycin Solution in Hurley I and II Hidradenitis Suppurativa: Results from Period A of RELIEVE, a Multicenter Randomized, Controlled Trial.

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy – a combination of intense pulsed light and radiofrequency – as an adjunct treatment to first-line therapies in Hurley stage I and II HS. <b><i>Methods:</i></b> The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either a…

Solidarity and transparency against the COVID ‐19 pandemic

Increased frequencies of CD11b+CD33+CD14+HLA-DRlowmyeloid-derived suppressor cells are an early event in melanoma patients

Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population characterized by immunosuppressive activity. Elevated levels of MDSC in peripheral blood are found in inflammatory diseases as well as in malignant tumors where they are supposed to be major contributors to mechanisms of tumor-associated tolerance. We investigated the frequency and function of MDSC in peripheral blood of melanoma patients and observed an accumulation of CD11b(+) CD33(+) CD14(+) HLA-DR(low) MDSC in all stages of disease (I-IV), including early stage I patients. Disease progression and enhanced tumor burden did not result in a further increase in frequencies or change in phenotype of MDSC. By investig…

Combined treatment of hidradenitis suppurativa with intense pulsed light (IPL) and radiofrequency (RF)

BACKGROUND Hidradenitis suppurativa is a chronic inflammatory disease with high burden. Treatment options are often unsatisfactory. We assessed the effect of a combination therapy of intense pulsed light (IPL) and radiofrequency (RF). METHODS The explorative study included 47 patients and was performed as a prospective, monocentric, randomized, three-arm parallel-group design trial with a prior 12 weeks observation period. Treatment arms were IPL and RF monotherapies or IPL + RF combination therapy. After 12 weeks, all patients received IPL + RF for additional 12 weeks (cross-over). Primary endpoint was the change in active lesion numbers, secondary endpoint the change in Dermatology Qualit…

Solution Properties and Potential Biological Applications of Zwitterionic Poly(ε-N-methacryloyl-l-lysine)

Poly(e-N-methacryloyl-l-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with Mw = 721 000 g mol–1. The polymer dissolves in pure water as well as in aqueous salt solution up to 5 M NaClO4 and over wide range of pH values (1.3 ≤ pH ≤ 12.7) as single chains without any sign for aggregate formation. The zwitterionic polymer shows an expanded random coil structure at and close to isoelectric conditions and further expands upon addition of acid and base, respectively. The polymer fulfills four major prerequisites for a promising nano carrier in potential biomedical applications: (1) It is biocompatible, indicated by a low cytotoxicity. (2) It does …

Selective RAR agonists for acne vulgaris: A narrative review.

Background Acne vulgaris is a chronic disfiguring inflammatory disease of adolescents and adults affecting up to 90% of the population around the world. The sequence of etiopathogenesis in acne is not completely understood but involves abnormalities in sebum production, follicular plugging, proliferation of propionibacterium acnes, and chronic inflammation. Aims This review aims to summarize the features of the topical selective RAR agonists in treating acne vulgaris with a special emphasis on the 4th generation topical retinoid trifarotene. Methods Studies were identified by searching electronic databases (MEDLINE and PubMed) till August 2019 and reference lists of respective articles. Onl…

Efficacy of 595- and 1319-nm pulsed dye laser in the treatment of acne vulgaris: a narrative review

Acne is one of the commonest problems of adolescence with almost half of the patients experiencing persistence into adulthood. Pulsed dye lasers (PDL) with wavelengths of 585 and 595 nm targeting hemoglobin have been used for the treatment of this condition and its sequelae. Recent introduction of PDL with a higher wavelength of 1319 nm has been reported to offer some benefit to acne patients. We reviewed the literature on the use of 595-nm and 1319-nm PDL in the management of acne. A PubMed literature search for search terms "pulsed dye laser," "acne laser therapy," "light therapy for acne," "595 nm and acne," "1319 nm and acne" was done. Studies, series and case reports were included. The…

Reconstitution of Myelomonocyte-Depleted Mice With Monocytes, But Not With Neutrophils, Reestablishes Arterial Hypertension and Oxidative Stress in Response To Angiogtensin II

Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.

Background Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine. Objective In this study we developed a human PBMC–engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms. Methods Nonobese diabetic (NOD)– scid -γc −/− mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically. Results Using the aeroallergens birch or gra…

Treatment of Axillary hyperhidrosis

BACKGROUND Axillary hyperhidrosis characterized by excessive sweating in the axillary regions is a frustrating chronic autonomic disorder leading to social embarrassment, impaired quality of life and usually associated with palmoplantar hyperhidrosis. Identifying the condition and its cause is central to the management. AIM The aim of this article is to discuss treatment options for axillary hyperhidrosis. METHODS Comprehensive literature search using PubMed and Google Scholar was performed to review relevant published articles related to diagnosis and treatment of axillary hyperhidrosis. RESULTS Treatment modalities for axillary hyperhydrosis vary from topical and systemic agents to inject…

Gram-positive bacteria on grass pollen exhibit adjuvant activity inducing inflammatory T cell responses.

BACKGROUND: Recently, it has been established that pollen grains contain Th2-enhancing activities besides allergens. OBJECTIVE: The aim of this study was to analyse whether pollen carry additional adjuvant factors like microbes and what immunological effects they may exert. METHODS: Timothy pollen grains were collected and disseminated on agar plates, and the growing microorganisms were cultivated and defined. Furthermore, the immunologic effects of microbial products on DC and T cell responses were analysed. RESULTS: A complex mixture of bacteria and moulds was detected on grass pollen. Besides Gram-negative bacteria that are known to favour Th1-directed immune responses, moulds were ident…

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study

Abstract Aims  Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Methods and results  Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was…

Editorial: Update Guidelines Dermatologic Oncology

Selective Uptake of Cylindrical Poly(2-Oxazoline) Brush-AntiDEC205 Antibody-OVA Antigen Conjugates into DEC-Positive Dendritic Cells and Subsequent T-Cell Activation

To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+) -positive mouse bone marrow-derived dendri…

Sodium chloride is an ionic checkpoint for human Th2 cell responses and shapes the atopic skin microenvironment

One sentence summarySodium is an ionic checkpoint for the induction and amplification of human Th2 cell responses and shapes the atopic skin microenvironment, where it could serve as a novel therapeutic target for Th2 mediated diseases.AbstractThere has been a strong increase in the incidence of allergic diseases over the last 50 years. Environmental factors most likely account for this phenomenon. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation, which is characteristic of atopic diseases, remains unclear. It has previously been reported that dietary sodium chloride promotes the polarization of Th17 cells with implications for aut…

Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma

The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual ‘on demand’ production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing. Successful trials have been performed by intranodal administration of sterile isotonic solutions of synthetic …

Immune checkpoint inhibitors: a milestone in the treatment of melanoma

Summary It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge – mostly acquired through animal experiments – could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life. With the advent of novel immunological approaches, the meaning of long-term survival as well as quality of life has been redefined for oncologic…

Immunotherapy of Malignant Melanoma

For the field of cancer immunotherapy, malignant melanoma has a very special role. It has certainly critically influenced the past and the present of the field. Research performed in malignant melanoma has started to shape the field of cancer immunotherapy more than 20 years ago with the discovery of the first tumor-associated antigens documented to be recognized by antigen-specific T cells in patients. As discussed in the following sections, the privileged role of malignant melanoma has not been restricted to the pioneering phase of initial antigen discovery but has continued to exist through more than 20 years as documented by the clinical successes reported for immunotherapies such as cy…

New diagnostic and imaging technologies in dermatology

INTRODUCTION Diagnosis of dermatological disorders is primarily based on clinical examination in combination with histopathology. However, clinical findings alone may not be sufficient for accurate diagnosis and cutaneous biopsies are being associated with morbidity. OBJECTIVE The objective of this article is to review the newer technologies along with their applications, limitation and future prospectus. METHODOLOGY Comprehensive literature search was performed using electronic online databases "PubMed" and "Google Scholar". Articles published in English language were considered for the review. RESULTS In order to improve and/or widen the armamentarium in dermatologic disease diagnosis and…

Merkel cell carcinoma‐derived Erysipelas carcinomatosum

Psoriasis: Embarking a dynamic shift in the skin microbiota

Recent interest has arisen regarding the role of microbiome and its composition in the pathogenesis of psoriasis. Numerous studies have shown that there are alterations in skin flora arrangement between normal individuals and psoriatic patients. Psoriasis exacerbation could be interconnected with epidermal or mucosal colonization with streptococci, Malassezia, Staphylococcus aureus, or Candida albicans. The role of cutaneous and gut microbiome in psoriasis pathogenesis has recently been studied in both human and animal models. In this review, we try to evaluate various pathogenic mechanisms linking the microbiota and psoriasis. The literature research included peer-reviewed articles which i…

Carboxytherapy in dermatology.

Abstract Carboxytherapy is a medical technique during which a sterile gas—carbon dioxide—is injected into the subdermal tissue. The utility of carbon dioxide injections has enhanced the practical relevance of carboxytherapy as a method for the management of multiple disorders. We have evaluated its use in the treatment of dermatologic conditions by searching electronic databases (ie, MEDLINE and PubMed) for contributions in the English language through January 2021. Carboxytherapy provides an attractive aesthetic option in skin rejuvenation, atrophic scars, striae distensae (stretch marks), cellulite-fibrolipodystrophy adhesions after liposuction, and certain types of alopecia. We discuss t…

Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition.

Aims Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel class of drugs for the treatment of hyperglycaemia. Preliminary evidence suggests that their antioxidant and anti-inflammatory effects may have beneficial effects on the cardiovascular complications of diabetes. In the present study, we investigate in an experimental sepsis model whether linagliptin exerts pleiotropic vascular effects independent of its glucose-lowering properties. Methods and results Linagliptin (83 mg/kg chow for 7days) was administered in a rat model of lipopolysaccharide (LPS) (10 mg/kg, single i.p. dose/24 h)-induced sepsis. Vascular relaxation, reactive oxygen species (ROS) formation, expression of NADPH oxida…

Brief S2k guidelines - Cutaneous squamous cell carcinoma

Nanoparticles and the immune system: challenges and opportunities

Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels

To target nanomedicines to specific cells, especially of the immune system, nanobodies can be considered as an attractive tool, as they lack the Fc part as compared to traditional antibodies and, thus, prevent unfavorable Fc-receptor mediated mistargeting. For that purpose, we have site-specifically conjugated CD206/MMR-targeting nanobodies to three types of dye-labeled nanogel derivatives: non-degradable nanogels, acid-degradable nanogels (with ketal crosslinks), and single polymer chains (also obtained after nanogel degradation). All of them can be obtained from the same reactive ester precursor block copolymer. After incubation with na&iuml

Emerging drugs for the treatment of vitiligo.

Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treat…

Simvastatin in vitiligo: an update with recent review of the literature.

Patients with vitiligo often seek medical attention, as it diminishes their quality of life resulting in significant morbidity. Several topical and systemic therapies are in vogue targeting the immunological aspect of this disease, but results are often unsatisfactory, and complete cure remains elusive. Recently, simvastatin, a 3-hydroxy-3-methylyglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is being evaluated for vitiligo management because of its multimodal action, easy availability, and low cost. The proposed multimodal actions range from anti-inflammatory, antioxidant, to immunomodulatory properties which may be of therapeutic benefit in vitiligo patients. The authors intend to eva…

Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities.

The introduction of small molecule BRAFV600 kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAFV600 inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAFV600 inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAFV600 inhibitors, evoking concern in cl…

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encod…

Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells

Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…

Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients

Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiothera…

Acanthosis nigricans: A review.

Background Acanthosis nigricans (AN) is a cutaneous disorder characterized by symmetric velvety hyperpigmented plaques on intertriginous areas like axilla, neck, inframammary, and groin. Aims To summarize the pathophysiology and classification of AN, provide an update of diagnostic testing strategies, and describe the current therapeutic options described so far in the literature for this disease. Methods A comprehensive english language literature search across multiple databases (PubMed, EMBASE, MEDLINE, and Cochrane) for keywords (alone and in combination) was performed. MeSH as well as non-MeSH terms such as "acanthosis nigricans," "classification," "pathophysiology," "diagnosis," "trea…

Asymptomatische, erworbene symmetrische Läsionen am Augeninnenwinkel

LFA-1 Contributes to Signal I of T-Cell Activation and to the Production of Th1 Cytokines

The beta(2) integrins are important for both transendothelial migration of leukocytes and T-cell activation during antigen presentation. In T cells, triggering of leukocyte functional antigen-1 (LFA-1) is required for full activation and T-helper (Th)1/Th2 differentiation. We used CD18-deficient (CD18(-/-)) mice to examine the role of LFA-1 in the activation of T cells. Compared with wild-type controls, CD18(-/-) T cells proliferated normally when stimulated with antibodies against CD3 and CD28, but secreted significantly less IFN-gamma and IL-2 than their wild-type counterparts. However, when T cells were stimulated with dendritic cells (DCs) that provide additional LFA-1 ligation, the pro…

Uptake and presentation of exogenous antigen and presentation of endogenously produced antigen by skin dendritic cells represent equivalent pathways for the priming of cellular immune responses following biolistic DNA immunization

Gene gun-mediated biolistic DNA vaccination with beta-galactosidase (betaGal)-encoding plasmid vectors efficiently modulated antigen-induced immune responses in an animal model of type I allergy, including the inhibition of immunoglobulin E (IgE) production. Here we show that CD4(+) as well as CD8(+) T cells from mice biolistically transfected with a plasmid encoding betaGal under the control of the fascin promoter (pFascin-betaGal) are capable of inhibiting betaGal-specific IgE production after adoptive transfer into naïve recipients. Moreover, suppression of IgE production was dependent on interferon (IFN)-gamma. To analyse the modalities of activation of CD4(+) and CD8(+) T cells regardi…

Angiotensin II-induced vascular dysfunction depends on interferon-γ-driven immune cell recruitment and mutual activation of monocytes and NK-cells.

Objective— Immune cells contribute to angiotensin II (ATII)–induced vascular dysfunction and inflammation. Interferon-γ (IFN-γ), an inflammatory cytokine exclusively produced by immune cells, seems to be involved in ATII-driven cardiovascular injury, but the actions and cellular source of IFN-γ remain incompletely understood. Approach and Results— IFN-γ −/− and Tbx21 −/− mice were partially protected from ATII-induced (1 mg/kg per day of ATII, infused subcutaneously by miniosmotic pumps) vascular endothelial and smooth muscle dysfunction, whereas mice overexpressing IFN-γ showed constitutive vascular dysfunction. Absence of T-box expressed in T cells (T-bet), the IFN-γ transcription factor…

Toward Anticancer Immunotherapeutics: Well-Defined Polymer-Antibody Conjugates for Selective Dendritic Cell Targeting

This paper describes the synthesis of semitelechelic maleimide-modified N-(2-hydroxypropyl)methacrylamid) (HPMA) based polymers of narrow dispersity that can be conjugated e.g. to anti-DEC-205 antibodies affording "star-like" topologies (one antibody decorated with several polymer chains). FCS revealed a hydrodynamic diameter of R(h)  = 7.9 nm and SEC narrow dispersity (1.45). Primary in vitro studies with bone marrow derived dendritic cells (DC) show higher cellular binding and uptake rates compared to control samples. Moreover, incubating these conjugates to primary splenocytes demonstrates a much higher affinity to the primary DCs than to any other immune cell population within the splee…

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivo…

Characterizing psychosocial distress in melanoma patients using the expert rating instrument PO-Bado SF

Background Although psychosocial distress has been evaluated well in cancer entities like breast or prostate cancer, its impact on melanoma patients still needs to be characterized. The objectives of this study were to (i) evaluate psychosocial distress in melanoma patients using an expert rating instrument [basic documentation for psycho-oncology short version (PO-Bado SF)]; (ii) determine associated demographic and clinical variables; and (iii) assess the acceptance of using PO-Bado SF as a routine procedure in a skin cancer unit. Methods A cross-sectional group of 696 melanoma patients was recruited. During the routine contact, doctors assessed the patients subjective distress using PO-B…

Past, present and future of immunology in Mainz.

Combined treatment of hidradenitis suppurativa with intense pulsed light (IPL) and radiofrequency (RF)

Background: Hidradenitis suppurativa is a chronic inflammatory disease with high burden. Treatment options are often unsatisfactory. We assessed the effect of a combination therapy of intense pulsed light (IPL) and radiofrequency (RF). Methods: The explorative study included 47 patients and was performed as a prospective, monocentric, randomized, three-arm parallel-group design trial with a prior 12 weeks observation period. Treatment arms were IPL and RF monotherapies or IPL + RF combination therapy. After 12 weeks, all patients received IPL + RF for additional 12 weeks (cross-over). Primary endpoint was the change in active lesion numbers, secondary endpoint the change in Dermatology Qual…