Exercise-Induced Metabolic Reprogramming and Immune Modulation: A Novel Strategy for Cancer Therapy.

Abstract

Exercise represents a non-pharmacological strategy capable of concurrently modulating tumor metabolism and immunity. Regular physical activity reprograms systemic and tumorlocalized metabolic networks, including glucose, lactate, amino acid, and lipid pathways, while enhancing innate and adaptive immune responses. Exercise-induced myokines (e.g., IL-6, IL-15, irisin, SPARC) and improved vascularization contribute to reshaping the tumor microenvironment (TME), mitigating immunosuppressive metabolite accumulation, and promoting T cell and NK cell infiltration. Mechanistically, exercise activates integrated signaling networks including AMPK-mTOR-HIF1α, PGC-1α-ERRα, and IL-6/STAT3 axes, supporting metabolic flexibility and anti-tumor immunity. Translational and clinical studies suggest exercise can enhance chemotherapy and immunotherapy efficacy, while precision exercise prescriptions based on FITT principles, biomarkers, and patient-specific tolerance may maximize therapeutic benefits. This review summarizes the molecular and systemic mechanisms of exercise-induced metabolic-immune reprogramming and outlines strategies for clinical translation in oncology.