Search results for "immunology and allergy"
showing 10 items of 2868 documents
Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts
2018
Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments. Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs). Expert commentary: It is evident that aPL induce a proinflamma…
Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis
2019
Abstract Neutrophil extracellular traps (NETs) are formed by polymorphonuclear neutrophils (PMN) and contribute to the innate host defense by binding and killing bacterial and fungal pathogens. Because NET formation depends on histone hypercitrullination by peptidylarginine deiminase 4 (PAD4), we used PAD4 gene deficient (Pad4-/-) mice in a mouse model of invasive pulmonary aspergillosis (IPA) to address the contribution of NETs to the innate host defense in vivo. After the induction (24 h) of IPA by i.t. infection with Aspergillus fumigatus conidia, Pad4-/- mice revealed lower fungal burden in the lungs, accompanied by less acute lung injury, TNFα and citH3 compared to wildtype controls. T…
Evaluation of tumor immune contexture among intrinsic molecular subtypes helps to predict outcome in early breast cancer
2021
BackgroundThe prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes.MethodsWe performed in silico analyses in more than 2800 early breast cancer transcriptomes with corresponding clinical annotations. We first developed a new gene expression deconvolution algorithm that accurately estimates the quantity of immune cell populations (tumor immune contexture,…
Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCO…
2020
BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.MethodsThis retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cS…
Expression profiles of HMGB1 on B-CLL related leukocytes contribute to prediction of relapse.
2020
The High Mobility Group Box 1 (HMGB1) is a nuclear protein that is frequently overexpressed in hematologic diseases and might be of relevance in immunogenic cancer control thus correlating with patients' (pts.) prognosis in diseases such as acute myeloid, acute lymphatic and chronic lymphocytic leukemia.Expression profiles of blasts from AML (n = 21), ALL (n = 16) and of B-lymphocytes of CLL (n = 9) pts. were analyzed for surface expression of HMGB1 using flow cytometry. Expression was quantified and correlated with clinically and prognostically relevant markers.Expression profiling of HMGB1 in blasts of AML and ALL subtypes did not show differences between primary vs. secondary disease dev…
Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a…
2020
Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA’s. Using specific cut-offs determined…
Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting
2018
The eighth annual conference of “Innovative therapy, monoclonal antibodies, and beyond” was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS–Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneit…
BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)
2017
Vγ9Vδ2 T cells are anti-tumor immune effectors of growing interest in cancer including Pancreatic Ductal Adenocarcinoma (PDAC), an especially aggressive cancer characterized by a hypoxic and nutrient-starved immunosuppressive microenvironment. Since Butyrophilin 3 A (BTN3A) isoforms are critical activating molecules of Vγ9Vδ2 T cells, we set out to study BTN3A expression under both basal and stress conditions in PDAC primary tumors, and in novel patient-derived xenograft and PDAC-derived cell lines. BTN3A2 was shown to be the most abundant isoform in PDAC and was stress-regulated. Vγ9Vδ2 T cells cytolytic functions against PDAC required BTN3A and this activity was strongly enhanced by the a…
Immunotherapy of colorectal cancer: New perspectives after a long path
2016
Although significant therapeutic improvement has been achieved in the last 10 years, the survival of metastatic colorectal cancer patients remains in a range of 28 to 30 months. Presently, systemic treatment includes combination chemotherapy with oxaliplatin and/or irinotecan together with a backbone of 5-fluorouracil/levofolinate, alone or in combination with monoclonal antibodies to VEGFA (bevacizumab) or EGF receptor (cetuximab and panitumumab). The recent rise of immune checkpoint inhibitors in the therapeutic scenario has renewed scientific interest in the investigation of immunotherapy in metastatic colorectal cancer patients. According to our experience and view, here, we review the…
CIMT 2018: Pushing frontiers in cancer immunotherapy — Report on the 16th Annual Meeting of the Association for Cancer Immunotherapy
2018
ABSTRACT The 16th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Europe’s largest meeting series of its kind, took place in Mainz, Germany from 15–17 May, 2018. Cutting-edge advancements in cancer immunotherapy were discussed among more than 700 scientists under the motto “Pushing Frontiers in Cancer Immunotherapy”. This meeting report is a summary of some of the CIMT 2018 highlights.