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

Anqi He1, Tianjie Bao1, Shunzi Rong1

  • 1Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China.

Exercise Immunology Review
|December 18, 2025
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Summary
This summary is machine-generated.

Regular exercise reprograms tumor metabolism and immunity by altering metabolic pathways and enhancing immune cell activity. This non-pharmacological approach shows promise for improving cancer treatments.

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Area of Science:

  • Oncology
  • Immunology
  • Metabolism
  • Exercise Science

Background:

  • Exercise is a potent non-pharmacological intervention impacting cancer biology.
  • Physical activity influences systemic and tumor-specific metabolic networks.
  • Exercise modulates both innate and adaptive immune responses within the tumor microenvironment.

Purpose of the Study:

  • To review the molecular and systemic mechanisms of exercise-induced metabolic and immune reprogramming in cancer.
  • To explore how exercise reshapes the tumor microenvironment (TME).
  • To outline strategies for the clinical translation of exercise interventions in oncology.

Main Methods:

  • Review of molecular signaling pathways activated by exercise, including AMPK-mTOR-HIF1α, PGC-1α-ERRα, and IL-6/STAT3.
  • Analysis of exercise-induced changes in systemic and tumor metabolism (glucose, lactate, amino acids, lipids).
  • Examination of exercise effects on immune cell infiltration and function (T cells, NK cells) and myokine release (IL-6, IL-15, irisin, SPARC).

Main Results:

  • Exercise reprograms metabolic pathways, enhancing metabolic flexibility and reducing immunosuppressive metabolites.
  • Exercise promotes anti-tumor immunity through myokine secretion and improved vascularization, leading to increased immune cell infiltration.
  • Exercise activates key signaling networks that integrate metabolic and immune functions.

Conclusions:

  • Exercise significantly reprograms the tumor metabolic and immune landscape, offering a non-pharmacological strategy to combat cancer.
  • Exercise interventions, particularly precision prescriptions, may enhance the efficacy of chemotherapy and immunotherapy.
  • Further clinical translation is warranted to optimize exercise-based cancer therapies.