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Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients

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Baitsch, Lukas | Baumgaertner, Petra | Devevre, Estelle | Raghav, Sunil | Legat, Amandine | Barba, Leticia | Wieckowski, Sébastien | Bouzourene, Hanifa | Deplancke, Bart | Romero, Pedro | Rufer, Nathalie | Speiser, Daniel

Edité par CCSD ; American Society for Clinical Investigation -

International audience. 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.

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