Dissection of T-cell antigen specificity in human melanoma
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Dissection of T-cell antigen specificity in human melanoma. / Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels; Skou, Rikke Birgitte Lyngaa; Donia, Marco; Ellebæk, Eva; Svane, Inge Marie; Schumacher, Ton N; Thor Straten, Per; Hadrup, Sine Reker.
In: Cancer Research, Vol. 72, No. 7, 2012, p. 1642-50.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2012
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
VL - 72
SP - 1642
EP - 1650
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -
ID: 48579963