研究人员发现，高脂饮食（HFD）诱导的肥胖会损害鼠肿瘤微环境（TME）中的CD8+T细胞功能，从而加速肿瘤的生长。研究人员在TME中生成了细胞代谢的单细胞分辨率图谱，并详细介绍了TME如何因饮食引起的肥胖而改变。研究人员发现，肿瘤和CD8+T细胞对肥胖表现出独特的代谢适应性。肿瘤细胞可通过HFD增加脂肪摄取，而浸润肿瘤的CD8+T细胞则不会。这些差异适应导致HFD肿瘤中的脂肪酸分配改变，从而损害CD8+T细胞的浸润和功能。阻止肥胖小鼠中肿瘤细胞的代谢重编程可提高抗肿瘤免疫力。对人类癌症的分析揭示了CD8+T细胞标志物的类似转录改变，这表明利用代谢进行干预可能改善癌症免疫疗法。
据了解，肥胖是主要的癌症危险因素，但尚不清楚全身代谢的差异如何改变TME并影响抗肿瘤免疫力。
附：英文原文
Title: Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity
Author: Alison E. Ringel, Jefte M. Drijvers, Gregory J. Baker, Alessia Catozzi, Juan C. García-Caaveras, 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
Issue&Volume: 2020-12-09
Abstract: Obesity is a major cancer risk factor, but how differences in systemic metabolismchange 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-cellresolution atlas of cellular metabolism in the TME, detailing how it changes withdiet-induced obesity. We find that tumor and CD8+ T cells display distinct metabolic adaptations to obesity. Tumor cells increase fatuptake with HFD, whereas tumor-infiltrating CD8+ T cells do not. These differential adaptations lead to altered fatty acid partitioningin HFD tumors, impairing CD8+ T cell infiltration and function. Blocking metabolic reprogramming by tumor cellsin obese mice improves anti-tumor immunity. Analysis of human cancers reveals similartranscriptional changes in CD8+ T cell markers, suggesting interventions that exploit metabolism to improve cancerimmunotherapy.
DOI: 10.1016/j.cell.2020.11.009
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31526-9