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Why the link between immune infiltration and tumor control varies so strongly across tissues remains unresolved. We propose the “immunometabolic gatekeeping” framework, whereby tissue-intrinsic metabolic activity and waste-handling capacity shape anti-tumour immunity. In high-flux tissues, metabolic stress impairs immune surveillance, decoupling infiltration from control and allowing tumor outgrowth. This framework explains cancer paradoxes—including T cell prognostic heterogeneity, hereditary and pediatric tumor tropisms, sex-biased tumor incidence, and cancer-resistant species—and suggests metabolism-aware strategies for cancer prevention and immunotherapy.
Why the link between immune infiltration and tumor control varies so strongly across tissues remains unresolved. We propose the “immunometabolic gatekeeping” framework, whereby tissue-intrinsic metabolic activity and waste-handling capacity shape anti-tumour immunity. In high-flux tissues, metabolic stress impairs immune surveillance, decoupling infiltration from control and allowing tumor outgrowth. This framework explains cancer paradoxes—including T cell prognostic heterogeneity, hereditary and pediatric tumor tropisms, sex-biased tumor incidence, and cancer-resistant species—and suggests metabolism-aware strategies for cancer prevention and immunotherapy.
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