Transient Dietary Stress and Tumor Immunity: From High-Fat Diet-Induced Ferroptotic Memory to Broader Immunometabolic Regulation

Qi Gong; Pengcheng Hu

Abstract

This perspective highlights the lasting impact of diet on tumor immunity, focusing on the long-term effects of transient high-fat diet (HFD) exposure. Short-term HFD alters CD8⁺ T-cell metabolism, causing lipid peroxidation and ferroptosis, thereby compromising antitumor immunity. The purine salvage pathway can enhance CD8⁺ T-cell antioxidant capacity, thereby partially reversing HFD-induced immune dysfunction, suggesting the metabolic reversibility of diet-induced immunosuppression. Meanwhile, other dietary components, such as high sugar, high salt, and high fiber, uniquely influence tumor immunity. Specifically, high-sugar diets promote immune evasion by upregulating PD-L1 and impairing CD8⁺ T-cell activation, high-salt intake enhances CD8⁺ T-cell effector responses under certain conditions, and high-fiber diets increase tumor-infiltrating T cells and enhance anti-PD-1 immunotherapy efficacy. These studies underscore the complexity of dietary influences on cancer immunity, suggesting that diet actively shapes immune memory and thus affects cancer progression.

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