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2011
- doi: 10.1172/JCI46102
- issn: 0021-9738
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info:eu-repo/semantics/altIdentifier/pmid/21555851
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info:eu-repo/semantics/altIdentifier/eissn/1558-8238
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_9E5EBEDCC14D4
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Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cellsCiter ce document
L. Baitsch et al., « Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients. », Serveur académique Lausannois, ID : 10.1172/JCI46102
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In chronic viral infections, CD8⁺ T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8⁺ T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8⁺ T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.