期刊
CELL
卷 176, 期 4, 页码 775-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.11.043
关键词
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资金
- Merck KGaA, Darmstadt, Germany
- Chan Zuckerberg Initiative (CZI)
- HHMI International Scholar Award
- European Research Council Consolidator Grant (ERC-COG) [724471-HemTree2.0]
- MRA Established Investigator Award [509044]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- KWF Queen Wilhelmina Award [NKI 2013-6122]
- ERC AdG SENSIT
- ERC (scAssembly)
- Flight Attendant Medical Research Institute (FAMRI)
- Helen and Martin Kimmel awards for innovative investigation
- SCA award of the Wolfson Foundation and Family Charitable Trust
- CZI
- Marie Curie Individual Fellowship (EU) [746382-SCALTIE]
- Rising Tide Foundation
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 TOR 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.
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