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-assoc...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (7), p.1642-1650
Main Authors: SICK ANDERSEN, Rikke, ALBAEK TRUE, Charlotte, JUNKER, Niels, LYNGAA, Rikke, DONIA, Marco, ELLEBAEK, Eva, SVANE, Inge Marie, SCHUMACHER, Ton N, THOR STRATEN, Per, REKER HADRUP, Sine
Format: Article
Language:English
Subjects:
Adoptive transfer
Antigens, Neoplasm - immunology
Antineoplastic agents
Biological and medical sciences
Cancer
Cell culture
Cells, Cultured
Dermatology
Differentiation
Epitopes
Epitopes, T-Lymphocyte
Humans
Interleukins
Lymphocytes T
Lymphocytes, Tumor-Infiltrating - immunology
Medical sciences
Melanoma
Melanoma - immunology
Melanoma-associated antigen
Pharmacology. Drug treatments
T-Cell Antigen Receptor Specificity - immunology
Tumor-infiltrating lymphocytes
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
Viruses - immunology
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-11-2614