Dissection of T-cell antigen specificity in human melanoma.
Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes predominantly from differentiation and cancer-testis antigens. Notably, the majority of these responses were of low frequency and tumor-specific T-cell frequencies decreased during rapid expansion. A further notable observation was a large variation in the T-cell specificities detected in cultures established from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined.
Department of Hematology, Center for Cancer Immune Therapy and Oncology, University Hospital Herlev, Herlev, Denmark.
Rikke Sick
RS
Andersen
Charlotte Albæk
CA
Thrue
Niels
N
Junker
Rikke
R
Lyngaa
Marco
M
Donia
Eva
E
Ellebæk
Inge Marie
IM
Svane
Ton N
TN
Schumacher
Per
P
Thor Straten
Sine Reker
SR
Hadrup
D000951:Antigens, Neoplasm / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D014780:Viruses / Q000276:immunology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte