0000000000181449
AUTHOR
Stefan Beissert
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(+…
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…
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…
Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis
Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system, and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to come into contact with the virus, it has been shown that the processing of viral antigens and the differentiation of antiviral CTLs are mediated by migratory CD103+ dermal DCs and CD8 alpha(+) lymph node resident DCs. In vivo regulatory T-cells (Tregs) are implicated in the regulation of antiviral immunity and we have shown that signaling via the receptor activ…
Comparison of pegylated interferon α-2b plus psoralen PUVA versus standard interferon α-2a plus PUVA in patients with cutaneous T-cell lymphoma
Objective The aim of this study was to evaluate the safety and efficacy profile of pegylated interferon α-2b (PEG-IFN α-2b) in combination with photochemotherapy (PUVA) in the treatment of cutaneous T-cell lymphoma (CTCL) in comparison with standard IFN α plus PUVA. Design Retrospective cohort study over a period of 7 years. Patients and interventions A total of 17 consecutive CTCL patients (stage IA–IV) were retrospectively analysed for toxicity and response rates associated with PEG-IFN α-2b (1.5 μg/kg weekly) plus PUVA (n = 9) or standard IFN α-2a (9 MIU 3×/week) plus PUVA (n = 8). Main outcome measures Differences of response rates (complete/partial remission), progression-free surv…
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…
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…