Immunometabolic Gatekeeping: Reconciling Peto's & the T-cell Infiltration Prognostic Paradox.

ABSTRACT: Classical models of cancer focus on tumour-intrinsic genetic aberrations and immune dynamics and often overlook how the metabolic environment of healthy tissues shapes tumour development and immune efficacy. Here, we propose that tissue-intrinsic metabolic intensity and waste-handling capacity act as an upstream gatekeeper of anti-tumour immunity, determining whether immune infiltration translates into effective immune function and safeguards the tissue from tumourigenesis. Across human cancers, tumours arising in high-metabolism tissues - like kidney, brain, and eye - tend to show high T cell infiltration but poor prognosis, suggesting pre-existing metabolic environments prior to malignant transformation may undermine immune function. This pattern is mirrored across species: large mammals

SUBMITTER: van den Berg NI 

PROVIDER: S-EPMC12676375 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature