Glycolipid metabolic crosstalk in tumor immune evasion and therapeutic targeting

Tumor immune evasion remains a major barrier to effective cancer immunotherapy and is closely associated with metabolic reprogramming. Glucose and lipid metabolism are highly interconnected processes that cooperatively reshape the tumor microenvironment (TME), regulate immune-cell function, and suppress anti-tumor immunity. Different from reviews that discuss tumor metabolism or immunometabolism as broad parallel topics, this review emphasizes glycolipid metabolic crosstalk as an integrated regulatory network linking metabolic flux, signaling pathways, lipid-derived mediators, and immune regulation. Key enzymes, metabolic intermediates, and signaling pathways, especially acetyl-CoA, NADPH, HIF-1α, and PI3K/Akt, act as central nodes that connect glucose utilization with lipid biosynthesis, redox homeostasis, epigenetic regulation, and immune escape. Therapeutic strategies targeting these pathways may enhance immunotherapy efficacy, but their effects are context dependent because metabolic interventions can simultaneously affect tumor cells and immune cells. A systems-level understanding of glycolipid metabolic networks, together with tumor-type-specific and immune-cell-specific analyses, may provide a basis for more precise metabolism-based cancer therapies.