The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines |
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Authors: | Rikke Bæk Sørensen Niels Junker Alexei Kirkin Heike Voigt Inge Marie Svane Jürgen C Becker Per thor Straten Mads Hald Andersen |
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Institution: | (1) Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev University Hospital, 2730 Herlev, Denmark;(2) Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany |
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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. |
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Keywords: | Melan-A/MART-1 Cytotox T-cells Melanoma Lysis Bcl-2 |
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