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Publication
Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor
Immunity.
Authors Ringel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM,
Miller BC, Juneja VR, Nguyen TH, Joshi S, Yao CH, Yoon H, Sage PT, LaFleur MW,
Trombley JD, Jacobson CA, Maliga Z, Gygi SP, Sorger PK, Rabinowitz JD, Sharpe
AH, Haigis MC
Submitted By Submitted Externally on 1/10/2022
Status Published
Journal Cell
Year 2020
Date Published 12/1/2020
Volume : Pages 183 : 1848 - 1866.e26
PubMed Reference 33301708
Abstract 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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