| Literature DB >> 30595452 |
Hanjie Li1, Anne M van der Leun2, Ido Yofe1, Yaniv Lubling3, Dikla Gelbard-Solodkin1, Alexander C J van Akkooi4, Marlous van den Braber2, Elisa A Rozeman5, John B A G Haanen5, Christian U Blank5, Hugo M Horlings6, Eyal David1, Yael Baran3, Akhiad Bercovich3, Aviezer Lifshitz3, Ton N Schumacher7, Amos Tanay8, Ido Amit9.
Abstract
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 CD8 T cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector "transitional" into a dysfunctional T cell state. CD8 T cells 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 CD8 T cells previously defined as exhausted are in fact a highly proliferating, clonal, and dynamically differentiating cell population within the human tumor microenvironment.Entities:
Keywords: T cell dysfunction; immune checkpoints; immunology; immunotherapy; melanoma; single-cell RNA-seq; tumor immunology; tumor microenvironment; tumor reactivity
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Year: 2018 PMID： 30595452 PMCID： PMC7253294 DOI： 10.1016/j.cell.2018.11.043
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582