Single-cell profiling of tumor-reactive CD4 + T-cells reveals unexpected transcriptomic diversity
Single-cell profiling of tumor-reactive CD4 + T-cells reveals unexpected transcriptomic diversity
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 has limited our ability to harness their activity. To address this issue, we have used single-cell mRNA sequencing to analyze the response of CD4+ T cells specific for a defined recombinant tumor antigen, both in the tumor microenvironment and draining lymph nodes (dLN). Designing new computational approaches to characterize subpopulations, we identify TIL transcriptomic patterns strikingly distinct from those elicited by responses to infection, and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes follicular helper (Tfh)-like 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 liver cancer and melanoma, in which it is negatively associated with response to checkpoint therapy. Our study unveils unsuspected differences between tumor and virus CD4+ T cell responses, and provides a proof-of-concept methodology to characterize tumor specific CD4+ T cell effector programs. Targeting these programs should help improve immunotherapy strategies. One Sentence SummarySingle-cell RNA sequencing reveals novel and highly diverse transcriptomic patterns characteristic of CD4+ T cell responses to tumors.
Nie Jia、Ciucci Thomas、Tamoutounour Samira、Mehta Monika、Hannenhalli Sridhar、Bosselut R¨|my、McGavern Dorian B.、Tran Bao、Magen Assaf、Zhao Yongmei
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of HealthLaboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of HealthMetaorganism Immunology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthCancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, National Institutes of HealthCenter for Bioinformatics and Computational Biology, University of Maryland, College ParkLaboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of HealthViral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthCancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, National Institutes of HealthLaboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health||Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health||Center for Bioinformatics and Computational Biology, University of Maryland, College ParkAdvanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, National Institutes of Health
肿瘤学基础医学细胞生物学
Nie Jia,Ciucci Thomas,Tamoutounour Samira,Mehta Monika,Hannenhalli Sridhar,Bosselut R¨|my,McGavern Dorian B.,Tran Bao,Magen Assaf,Zhao Yongmei.Single-cell profiling of tumor-reactive CD4 + T-cells reveals unexpected transcriptomic diversity[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/543199.点此复制
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