STAT3 Activation-Induced Fatty Acid Oxidation in CD8⁺ T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth.

ABSTRACT: Although obesity is known to be critical for cancer development, how obesity negatively impacts antitumor immune responses remains largely unknown. Here, we show that increased fatty acid oxidation (FAO) driven by activated STAT3 in CD8⁺ T effector cells is critical for obesity-associated breast tumor progression. Ablating T cell Stat3 or treatment with an FAO inhibitor in obese mice spontaneously developing breast tumor reduces FAO, increases glycolysis and CD8⁺ T effector cell functions, leading to inhibition of breast tumor development. Moreover, PD-1 ligation in CD8⁺ T cells activates STAT3 to increase FAO, inhibiting CD8⁺ T effector cell glycolysis and functions. Finally, leptin enriched in mammary adipocytes and fat tissues downregulates CD

SUBMITTER: Zhang C 

PROVIDER: S-EPMC6949402 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature