Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes.
We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines.
Topalian
S L
SL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Hom
S S
SS
Kawakami
Y
Y
Mancini
M
M
Schwartzentruber
D J
DJ
Zakut
R
R
Rosenberg
S A
SA
D000951:Antigens, Neoplasm / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D014162:Transfection; D014612:Vaccines
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D014612:Vaccines