Abstract：
:Most current tumor immunotherapy strategies leverage cytotoxic CD8+ T cells. Despite evidence for clinical potential of CD4+ 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 CD4+ 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 CD4+ T cell effector programs. Targeting these programs should help improve immunotherapy strategies.
journal_name
Cell Repjournal_title
Cell reportsauthors
Magen A,Nie J,Ciucci T,Tamoutounour S,Zhao Y,Mehta M,Tran B,McGavern DB,Hannenhalli S,Bosselut Rdoi
10.1016/j.celrep.2019.10.131subject
Has Abstractpub_date
2019-12-03 00:00:00pages
3019-3032.e6issue
10issn
2211-1247pii
S2211-1247(19)31464-0journal_volume
29pub_type
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