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.
2012-04-04
Eng.
Cancer research
Department of Hematology, Center for Cancer Immune Therapy and Oncology, University Hospital Herlev, Herlev, Denmark.
Cancer Res. 2012 Apr;72(7):1642-50
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