期刊
CELL REPORTS
卷 29, 期 10, 页码 3019-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.10.131
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类别
资金
- NCI Office of Science and Technology Resources
- Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH
Most current tumor immunotherapy strategies leverage cytotoxic CD8(+) T cells. Despite evidence for clinical potential of CD8(+) tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD8(+) TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD8(+) T cell effector programs. Targeting these programs should help improve immunotherapy strategies.
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