Dissection of T-cell antigen specificity in human melanoma

TY - JOUR

T1 - Dissection of T-cell antigen specificity in human melanoma

AU - Andersen, Rikke Sick

AU - Albæk Thrue, Charlotte

AU - Junker, Niels

AU - Skou, Rikke Birgitte Lyngaa

AU - Donia, Marco

AU - Ellebæk, Eva

AU - Svane, Inge Marie

AU - Schumacher, Ton N

AU - Thor Straten, Per

AU - Hadrup, Sine Reker

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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.

AB - 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.

U2 - 10.1158/0008-5472.can-11-2614

DO - 10.1158/0008-5472.can-11-2614

M3 - Journal article

C2 - 22311675

SN - 0008-5472

VL - 72

SP - 1642

EP - 1650

JO - Cancer Research

JF - Cancer Research

IS - 7

ER -