肿瘤微环境
生物
CD8型
细胞毒性T细胞
癌症研究
免疫
免疫疗法
免疫系统
肿瘤进展
癌症
脂肪组织
免疫学
内分泌学
生物化学
遗传学
体外
作者
Alison E. Ringel,Jefte M. Drijvers,Gregory J. Baker,Alessia Catozzi,Juan Carlos García-Cañaveras,Brandon M. Gassaway,Brian C. Miller,Vikram R. Juneja,Thao H. Nguyen,Shakchhi Joshi,Cong-Hui Yao,Haejin Yoon,Peter T. Sage,Martin W. LaFleur,Justin D. Trombley,Connor A. Jacobson,Zoltan Maliga,Steven P. Gygi,Peter K. Sorger,Joshua D. Rabinowitz,Arlene H. Sharpe,Marcia C. Haigis
出处
期刊:Cell
[Elsevier]
日期:2020-12-01
卷期号:183 (7): 1848-1866.e26
被引量:350
标识
DOI:10.1016/j.cell.2020.11.009
摘要
Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8+ T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. We find that tumor and CD8+ T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8+ T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8+ T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8+ T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy.
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