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Melanoma-specific T cells can occur spontaneously or in response to vaccination or other therapies, but the frequency is much lower than observed in viral infections. The presence of tumor-specific T cells does not necessarily translate into clinical regressions for a variety of reasons such as an insufficient frequency, activation state or homing capacity of the T cells or escape strategies of the tumor. Having screened melanoma patients prior to inclusion in vaccination trials for spontaneous tumor-specific T cells either by Elispot or tetramer-staining, we have identified 3 patients with sufficient numbers of tumor-reactive T cells to more than 1 TAA and at least 1 virus-antigen to perform phenotypic and functional analysis directly ex vivo. These stage IV melanoma patients showed specific CTL against melan-A.A2, tyrosinase.A2 and influenza matrix peptide (IMP).A2 readily detectable in peripheral blood. T-cell receptor (TCR) staining using the tetramer technology was combined with phenotypic characterization and functional assays. In contrast to IMP-specific CTL, melanoma-specific CTL were predominantly terminally differentiated effector cells. However, analysis of melan-A- and tyrosinase-specific T-cell lines showed that only a part of the melanoma-specific CTL were able to lyse peptide-loaded target cells. Interestingly, the described phenotypic and functional differences of melan-A- and tyrosinase-specific CTL appeared not only between patients but were also evident within patients, suggesting that the immune response against various tumor antigens is regulated independently.

Original publication

DOI

10.1002/ijc.20901

Type

Journal article

Journal

Int J Cancer

Publication Date

20/06/2005

Volume

115

Pages

450 - 455

Keywords

Adult, Aged, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Female, HLA-A Antigens, HLA-A2 Antigen, Humans, Immunophenotyping, MART-1 Antigen, Male, Melanoma, Middle Aged, Neoplasm Proteins, Peptide Fragments, Phenotype, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured