Regular and Acute Physical Activity and Cancer Immunity

Table of Contents

  1. Epidemiological Evidence
  2. Muscle Tissue and Immunity
  3. Immune Effects of Acute Exercise on Cancer Immunity
  4. Effects of Regular Training on Tumor Immunity
  5. Clinical Implications
  6. References
  7. One-Minute-Paper Topics

1 Epidemiological Evidence

Regular physical activity is associated with lower cancer incidence and mortality as well as lower tumor recurrence rates. Approximately half of all cancer deaths could be prevented through modification of lifestyle and environmental factors. Physical inactivity has reached pandemic proportions — nearly one in three adults worldwide does not meet WHO recommendations (Fiuza-Luces et al. 2023).

2 Muscle Tissue and Immunity

Skeletal muscle functions as an endocrine organ that releases myokines during contraction. IL-6 as the most prominent myokine increases exponentially during exercise and triggers an anti-inflammatory effect: induction of IL-1RA and IL-10, reduction of TNF. Muscular IL-6 can stimulate NK cells to be mobilized into the bloodstream and infiltrate tumors. Muscle wasting (sarcopenia) is associated with worse prognoses in cancer patients (Fiuza-Luces et al. 2023).

3 Immune Effects of Acute Exercise on Cancer Immunity

Acute exercise preferentially mobilizes effector lymphocytes with high cytotoxic potential (NK cells, CD8⁺ T cells, γδ T cells). The mobilized NK cells utilize their described cytotoxic mechanisms — granule exocytosis and TRAIL-mediated apoptosis — for the recognition and destruction of malignantly transformed cells, with the absence of MHC-I on tumor cells favoring NK cell activation (Murphy and Weaver 2016). These cells show anti-tumor transcriptional profiles and enhanced graft-versus-leukemia effects in xenograft mouse models (Batatinha et al. 2023; Fiuza-Luces et al. 2023).

4 Effects of Regular Training on Tumor Immunity

Preclinical studies show that regular training delays tumor progression. Mechanisms include:

  • Enhanced tumor infiltration: Increased infiltration of NK cells and CD8⁺ T cells into tumors through epinephrine-induced mobilization and IL-6-mediated redistribution
  • Reduction of regulatory T cells (Tregs): Decrease in immunosuppressive cells and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment
  • Improvement of T cell function: Reduction of T cell exhaustion and improvement of T cell repertoire diversity
  • Metabolic reprogramming: Lactate from working muscles may improve stemness properties of CD8⁺ T cells

5 Clinical Implications

There is increasing evidence that immune cells obtained from post-exercise blood could be used as adoptive cell therapy in cancer. The combination of physical activity with immunotherapies (e.g., checkpoint inhibitors) is a promising area of research (Fiuza-Luces et al. 2023).

References

  • Batatinha H et al. (2023) Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile. Front Immunol 14:1067369.
  • Fiuza-Luces C et al. (2023) The effect of physical exercise on anticancer immunity. Nat Rev Immunol.
  • Murphy K, Weaver C (2016) Janeway’s Immunobiology, 9th edn. Garland Science.

One-Minute-Paper Topics

A One-Minute-Paper (OMP) is a short, focused prompt that students answer in ~60 seconds at the end of a session to consolidate learning, surface misconceptions, and provide formative feedback. When answering, be concise, specific, and use terminology from today’s session.

  1. Summarise in one sentence the epidemiological evidence linking physical activity and reduced cancer risk.
  2. Which cancer entities show the strongest inverse association with physical activity?
  3. Explain the role of myokines in the anti-cancer effects of exercise.
  4. How does acute exercise mobilise NK cells, and why is this clinically interesting?
  5. What is the role of CD8⁺ T cells in tumour immune surveillance?
  6. Describe the function of γδ T cells and why they are relevant in exercise oncology.
  7. Define tumour immune infiltration and explain its prognostic value.
  8. How might exercise improve the efficacy of immune checkpoint inhibitors?
  9. What is adoptive cell transfer, and how could exercise enhance it?
  10. Explain one mechanism by which IL-6 from skeletal muscle could affect tumour growth.
  11. Why is the timing of exercise relative to chemotherapy a current research question?
  12. How do exercise-induced catecholamines influence NK cell trafficking?
  13. Name one well-conducted clinical trial of exercise as adjunct cancer therapy and its main finding.
  14. What is the difference between exercise as prevention and exercise as treatment in oncology?
  15. Which cancer patient groups might be at risk from intense exercise prescriptions?
  16. What was today’s most clinically actionable insight?
  17. Which concept from today’s lecture do you still find unclear?
  18. How would you design a feasibility study of high-intensity interval training in breast cancer survivors?
  19. Name one ethical consideration when prescribing exercise during active cancer treatment.
  20. What is one open question in exercise oncology you would like to investigate?