Research Overview

Treatment of advanced metastatic melanoma has for decades been a story of limited clinical success. This dramatically changed with the recent clinical implementation of two types of therapies: immunotherapy based on immunomodulating antibodies, termed immune checkpoint blocking therapy (ICBT), and targeted therapies employing inhibitors of the oncogenic MAPK signaling pathway. Those treatments can induce remarkable clinical responses in a subgroup of patients, but still the majority of patients is resistant to therapy or develops resistance after initial therapy response. There is accumulating evidence for a fundamental role of adaptive and innate cytotoxic lymphocytes, tumor antigen-specific T cells and natural killer (NK) cells, respectively, in tumor cell elimination not only in the course of immunotherapy but also targeted therapy. Both, adaptive and innate lymphocytes can recognize melanoma cells as “abnormal self” but by different mechanisms. Within the research group “Molecular Tumor Immunology” we study the interaction of melanoma cells with tumor antigen-specific CD4+ / CD8+ T cells and NK cells. In particular we focus on resistance mechanisms allowing tumor cells to escape either from recognition or killing by T cells and NK cells (immune escape). Our own studies suggest that melanoma immune escape sets a barrier to successful ICBT and targeted therapy indicating the need to unravel the underlying molecular resistance mechanisms for improvement of treatment regimens.
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