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

来源：

CANCER CELL | 2023年 / 41卷 / 09期

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

页码：1662 / +

页数：26

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