The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines.
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.
Sørensen
Rikke Baek
RB
Department of Hematology, Center for Cancer Immune Therapy (CCIT), Herlev University Hospital, Herlev, Denmark.
Junker
Niels
N
Kirkin
Alexei
A
Voigt
Heike
H
Svane
Inge Marie
IM
Becker
Jürgen C
JC
thor Straten
Per
P
Andersen
Mads Hald
MH
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D045744:Cell Line, Tumor / Q000737:chemistry / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis* / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008545:Melanoma / Q000737:chemistry* / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000276:immunology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; C527085:KLRK1 protein, human; C105787:MART-1-Melan-A(27-35) epitope; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes