Baitsch, LukasBaumgaertner, PetraDevevre, EstelleRaghav, Sunil K.Legat, AmandineBarba, LeticiaWieckowski, SebastienBouzourene, HanifaDeplancke, BartRomero, PedroRufer, NathalieSpeiser, Daniel E.2011-12-162011-12-162011-12-16201110.1172/JCI46102https://infoscience.epfl.ch/handle/20.500.14299/74021WOS:000291234300033In 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.Chronic Viral-InfectionEffector FunctionMolecular SignatureExpression ProfilesVirus-InfectionResponsesPersistenceTolerancePd-1Vaccinationtext::journal::journal article::research article