Article: article from journal or magazin.
Circulating Tumor-reactive CD8(+) T cells in melanoma patients contain a CD45RA(+)CCR7(-) effector subset exerting ex vivo tumor-specific cytolytic activity.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
To defend the host from malignancies, the immune system can spontaneously raise CD8(+) T-cell responses against tumor antigens. Investigating the functional state of tumor-reactive cytolytic T cells in cancer patients is a key step for understanding the role of these cells in tumor immunosurveillance and for evaluating the potential of immunotherapeutic approaches of vaccination against cancer. In this study we identified a subset of circulating tumor-reactive CD8(+) T lymphocytes, which specifically secreted IFN-gamma after exposition to autologous tumor cell lines in stage IV metastatic melanoma patients. Additional phenotypic characterization using multicolor flow cytometry revealed that a significant fraction of these cells were CD45RA(+)CCR7(-), a phenotype that has been proposed recently to characterize cytolytic effectors potentially able to home into inflamed tissues. In the case of an HLA-A2-expressing patient, the antigen specificity of this population was identified by using HLA-A2/peptide multimers incorporating a tyrosinase-derived peptide. Consistently with their phenotypic characteristics, A2/tyrosinase peptide multimer(+) CD8(+) T cells, isolated by cell sorting, were directly lytic ex vivo and able to specifically recognize tyrosinase-expressing tumor cells. Overall, these results provide the first evidence that a proportion of melanoma patients have circulating tumor-reactive T cells, which are lytic effectors cells.
Antigens, CD45/blood, Antigens, CD45/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte/immunology, HLA-A2 Antigen/immunology, Humans, Lymphocyte Activation/immunology, Melanoma/blood, Melanoma/immunology, Monophenol Monooxygenase/immunology, Receptors, CCR7, Receptors, Chemokine/blood, Receptors, Chemokine/immunology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, T-Lymphocytes, Regulatory/cytology, T-Lymphocytes, Regulatory/immunology
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