Abstract
Among the relatively large number of known tumor-associated antigens (TAA) which are recognized by human CD8 T-cells, Melan-A/MART-1 is one of the most-if not the most-frequently used target for anti-cancer vaccines in HLA-A2 + melanoma patients. In this study, we analyzed the killing of a large panel of melanoma cells by a high avidity, MART-1-specific T-cell clone or a MART-1-specific, polyclonal T-cell culture. Strikingly, we observed that the MART-1-specific T-cells only killed around half of the analyzed melanoma cell lines. In contrast a Bcl-2-specific T-cell clone killed all melanoma cell lines, although the T-cell avidity of this clone was significantly lower. The MART-1-specific T-cell clone expressed NKG-2D and was fully capable of releasing both perforin and Granzyme B. Notably, the resistance to killing by the MART-1-specific T-cells could be overcome by pulsing of the melanoma cells with the MART-1 epitope. Thus, the very frequently used MART-1 epitope was not expressed on the surface of many melanoma cell lines. Our data emphasize that the selected tumor antigens and/or epitopes are critical for the outcome of anti-cancer immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / analysis*
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Antigens, Neoplasm / immunology
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Antigens, Surface / analysis*
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Antigens, Surface / immunology
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Cell Line, Tumor / chemistry
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Cell Line, Tumor / immunology
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic
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Epitopes / analysis*
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Epitopes / immunology
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Epitopes, T-Lymphocyte / analysis*
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Epitopes, T-Lymphocyte / immunology
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Granzymes / biosynthesis
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Granzymes / immunology
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HLA-A2 Antigen / immunology*
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Humans
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Immunodominant Epitopes / analysis*
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Immunodominant Epitopes / immunology
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Interferon-gamma / metabolism
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Melanoma / chemistry*
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Melanoma / immunology
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NK Cell Lectin-Like Receptor Subfamily K / biosynthesis
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NK Cell Lectin-Like Receptor Subfamily K / immunology
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Neoplasm Proteins / analysis*
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Neoplasm Proteins / immunology
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Perforin
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Pore Forming Cytotoxic Proteins / biosynthesis
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Pore Forming Cytotoxic Proteins / immunology
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Proto-Oncogene Proteins c-bcl-2 / immunology
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Antigens, Neoplasm
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Antigens, Surface
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Epitopes
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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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Immunodominant Epitopes
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KLRK1 protein, human
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MART-1-Melan-A(27-35) epitope
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NK Cell Lectin-Like Receptor Subfamily K
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Neoplasm Proteins
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PRF1 protein, human
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Pore Forming Cytotoxic Proteins
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Proto-Oncogene Proteins c-bcl-2
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Perforin
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Interferon-gamma
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Granzymes