Tumor immunogenicity dictates reliance on TCF1 in CD8+T cells for response to immunotherapy

被引:35
作者
Escobar, Giulia [1 ,2 ]
Tooley, Katherine [1 ,2 ,3 ]
Oliveras, Joan Pages [1 ,2 ]
Huang, Linglin [1 ,2 ]
Cheng, Hanning [1 ,2 ]
Bookstaver, Michelle L. [1 ,2 ]
Edwards, Camilla [5 ]
Froimchuk, Eugene [5 ]
Xue, Chang [1 ,2 ]
Mangani, Davide [1 ,2 ]
Krishnan, Rajesh K. [1 ,2 ]
Hazel, Natanael [1 ,2 ]
Rutigliani, Carola [1 ,2 ]
Jewell, Christopher M. [5 ,6 ]
Biasco, Luca [4 ]
Anderson, Ana C. [1 ,2 ]
机构
[1] Harvard Med Sch, Ann Romney Ctr Neurol Dis, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Boston, MA 02115 USA
[3] Harvard Med Sch, Div Med Sci, Boston, MA USA
[4] UCL, Great Ormond St Inst Child Hlth, London, England
[5] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA
[6] VA Maryland Hlth Care Syst, US Dept Vet Affairs, Baltimore, MD 21201 USA
关键词
CD8(+) T-CELLS; IMMUNITY;
D O I
10.1016/j.ccell.2023.08.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Stem-like CD8+ T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1+CD8+ T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen specific CD8+ T cells and ICB response in poorly immunogenic tumors that accumulate TOX+ dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors. Importantly, improving T cell priming by vaccination or by enhancing antigen presentation on tumors rescues the defective responses of TCF1-deficient CD8+ T cells upon ICB in poorly immunogenic tumors. Our study highlights TCF1's role during the early stages of anti-tumor CD8+ T cell responses with important implications for guiding optimal therapeutic interventions in cancers with low TCF1+CD8+ T cells and low-neo-antigen expression.
引用
收藏
页码:1662 / +
页数:26
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