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 tumor-localized 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-HIF1 alpha, PGC-1 alpha-ERR alpha, 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.