Dissection of T-cell antigen specificity in human melanoma

Rikke Sick Andersen, Charlotte Albæk Thrue, Niels Junker, Rikke Birgitte Lyngaa, Marco Donia, Eva Ellebæk, Inge Marie Svane, Ton N. Schumacher, Per Thor Straten, Sine Reker Hadrup

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Abstract

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 melanomarestricted 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 AACR.
Original languageEnglish
JournalCancer Research
Volume72
Issue number7
Pages (from-to)1642-1650
Number of pages9
ISSN0008-5472
DOIs
Publication statusPublished - 2012
Externally publishedYes

Cite this

Andersen, R. S., Thrue, C. A., Junker, N., Lyngaa, R. B., Donia, M., Ellebæk, E., Svane, I. M., Schumacher, T. N., Straten, P. T., & Hadrup, S. R. (2012). Dissection of T-cell antigen specificity in human melanoma. Cancer Research, 72(7), 1642-1650. https://doi.org/10.1158/0008-5472.can-11-2614