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Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma.

Li, Hanjie; van der Leun, Anne M; Yofe, Ido; Lubling, Yaniv; Gelbard-Solodkin, Dikla; van Akkooi, Alexander C J; van den Braber, Marlous; Rozeman, Elisa A; Haanen, John B A G; Blank, Christian U; Horlings, Hugo M; David, Eyal; Baran, Yael; Bercovich, Akhiad; Lifshitz, Aviezer; Schumacher, Ton N; Tanay, Amos; Amit, Ido.
Cell; 176(4): 775-789.e18, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30595452
Tumor immune cell compositions play a major role in response to immunotherapy, but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here, we identify conserved intratumoral CD4 and CD8cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8cells showing continuous progression from an early effector "transitional" into a dysfunctional T cell state. CD8cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor reactivity. Our data demonstrate that CD8cells previously defined as exhausted are in fact a highly proliferating, clonal, and dynamically differentiating cell population within the human tumor microenvironment.
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