Phänotypische und funktionelle Charakterisierung von zytotoxischen T-Lymphozyten gegen Melanom-assoziierte Antigene bei gesunden Individuen und bei Melanompatienten vor und nach Peptidvakzinierung

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Powerful systemic and local T cell based immune responses against melanoma-associated antigens have been repeatedly identified in humans. New developments now greatly facilitate the analysis of tumor-specific cytotoxic T cells (CTL), although detectable immune responses are rarely sufficient to arrest tumor growth as apparent by the grim prognosis of advanced melanoma. Furthermore, very little is known about distinct phenotypes of CTL that have recently been found in melanoma patients and even healthy individuals. In the first part of the proposed work, the applicant will phenotypically and functionally characterize T cells reactive against the self-antigen Melan-A/MART-1 that are detectable at high levels in two thirds of normal HLA-A2 healthy blood donors. In the second part, the different functional stages of CTL in sentinel lymph nodes and peripheral blood specimens of melanoma patients before and after peptide-based vaccination will be studied. Taken together, the proposed work will provide important information in our understanding of the dynamics of the specific CTL response to tissue-specific self antigens under both physiological and pathological circumstances and will help to improve the design of specific immunotherapeutical approaches to cancer.