Metabolic reprogramming and immune evasion in cancer: mechanisms, therapeutic strategies, and clinical outlook

He Yuwei; Cui Jiuwei

doi:10.16689/j.cnki.cn11-9349/r.2026.04.001

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Electronic Journal of Metabolism and Nutrition of Cancer ›› 2026, Vol. 13 ›› Issue (4) : 457-464. DOI: 10.16689/j.cnki.cn11-9349/r.2026.04.001

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Metabolic reprogramming and immune evasion in cancer: mechanisms, therapeutic strategies, and clinical outlook

He Yuwei, Cui Jiuwei

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Abstract

The complex metabolic network in the tumor microenvironment (TME) plays a key role in controlling the growth and spread of malignant tumor cells, and it is closely linked to the function of infiltrating immune cells. Through metabolic reprogramming, tumor cells remodel the TME, leading to low oxygen, local acidity, nutrient depletion, and buildup of metabolic waste. This metabolic imbalance directly weakens the metabolic capacity and effector functions of infiltrating immune cells. In turn, the metabolic remodeling of immune cells further strengthens the immunosuppressive state of the TME, promoting tumor immune escape. Additionally, TME metabolites systematically reshape the genome through epigenetic modifications, speeding up T cell exhaustion and reinforcing the immunosuppressive features of the TME. Targeting metabolic pathways to provide metabolic intervention strategies for clinical anti-cancer therapy is currently under exploration. However, the high heterogeneity of tumors and the diversity of metabolic pathways present major challenges for translating these therapies into clinical practice. This review systematically outlines the molecular mechanisms by which metabolic reprogramming in the TME drives immune escape, summarizes the metabolic-epigenetic immune regulatory network, and provides a comprehensive overview of current metabolism-targeted therapeutic approaches, aiming to provide a reference for developing new anti-tumor immunometabolic strategies.

Key words

Immunometabolism / Tumor microenvironment / Metabolic reprogramming / Epigenetics / Targeted therapy / Immunotherapy

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He Yuwei, Cui Jiuwei. Metabolic reprogramming and immune evasion in cancer: mechanisms, therapeutic strategies, and clinical outlook[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(4): 457-464 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.04.001

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