Exercise Boosts the Immune System and Enhances Immunotherapy Responses in Pancreatic Cancer and Mesothelioma

Our plain-English summary of Exercise Boosts the Immune System and Enhances Immunotherapy Responses in Pancreatic Cancer and Mesothelioma, by B. Hapuarachi, S. Danson, J. Wadsley, et al (Biomolecules, 2026).

The study

• Authors: B. Hapuarachi, S. Danson, J. Wadsley, H. Brown, P. Southam, M. Muthana
• Journal: Biomolecules
• Published: 2026;16(4)
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Exercise modulates the immune system and may enhance anti-cancer activity, offering potential synergy with cancer immunotherapy. Tumours with low immune cell infiltration ("cold" tumours) often respond poorly to immunotherapy and are associated with poor prognosis. Here, we demonstrate that exercise can reshape the immune landscape of tumours across the cold spectrum.

Methods: C57BL/6 mice underwent orthotopic implantation of PANC02 (murine pancreatic adenocarcinoma) cells and BALB/c mice underwent intraperitoneal injections of AB-1 (murine mesothelioma) cells. Mice were then divided into groups; exercise with anti-Programmed Cell Death Protein 1 (PD-1), exercise with isotype, no exercise with anti-PD-1 and no exercise with isotype. Treadmill-running was performed for 20 min/day, 4 days/week at a speed of 12 metres/minute. Resistance training consisted of hanging upside down on a wire-mesh screen for 1 min 2 days/week. Flow cytometry was used to measure TME immune populations. Tumour and liver samples were harvested, paraffin wax-embedded/sectioned and analysed using SlideViewer 2.9.0™. A total of 22 healthy volunteers underwent a single bout of high-intensity interval cycling. Blood was collected pre- and post-exercise. Flow cytometry was used to measure leucocyte subpopulations. MSTO-211H (mesothelioma) and PANC-1 (pancreatic cancer) cells were cultured with pre- and post-exercise serum, with/without HSV1716, and viability determined using alamarBlue®. PANC-1 apoptosis and migration were assessed using caspase-3/7 and scratch assays, respectively.

Results: In an orthotopic pancreatic cancer mouse model, combining exercise with immunotherapy significantly increased tumour necrosis and reduced metastatic potential. In both pancreatic cancer and mesothelioma models, this combination remodelled the tumour microenvironment, enhancing cytotoxic CD8+ T cell infiltration, upregulating Programmed Cell Death Protein 1 (PD-1), and reducing Myeloid-Derived Suppressor Cells and regulatory T cells (Tregs). Complementary human studies revealed an acute systemic release of Natural Killer cells and a reduction in Tregs following high-intensity interval exercise in healthy volunteers. Moreover, exercise-conditioned serum from these participants exerted anti-cancer effects on pancreatic cancer and mesothelioma cell lines.

Conclusions: Altogether, these findings highlight exercise as a promising adjunct to immunotherapy for poorly immunogenic cancers such as pancreatic cancer and mesothelioma.

In plain English

This article reported mouse experiments, cell experiments and a small healthy-volunteer study of whether exercise changes immune responses to pancreatic cancer and mesothelioma. It did not study asbestos exposure. A 12-mouse pancreatic cancer pilot compared treadmill running, screen-hanging or both with no exercise. In the main studies, mice implanted with pancreatic cancer cells (20) or injected in the abdomen with mesothelioma cells (24) did both exercises or none. They received anti-PD1 immunotherapy or an inactive comparison antibody. In the mesothelioma mice, the exercise plus anti-PD1 group had more cytotoxic CD8+ T cells in tumours than either non-exercising group. Differences in tumour light signal and other immune cells were not statistically significant. In the pancreatic cancer mice, exercise was linked to fewer liver metastases and fewer immune-suppressing cells in tumours. Of 22 healthy volunteers, 20 had paired results. Their natural killer cells rose 32.6% (95% confidence interval 23.0% to 42.2%) after one intense cycling session. Post-exercise serum reduced migration of mesothelioma cells in the laboratory. The authors concluded that moderate-intensity exercise combined with anti-PD1 increased tumour necrosis, reduced metastatic disease and shifted the tumour environment toward a 'hot' state.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiments in mouse models of pancreatic cancer and mesothelioma; a before-and-after blood study in healthy volunteers; and in vitro cell-culture experiments
• Who was studied: Pancreatic cancer models: a pilot study of 12 C57BL/6 mice and a larger study of 20 C57BL/6 mice with PANC02 tumour cells implanted in the pancreas. Mesothelioma model: 24 BALB/c mice given intraperitoneal injections of AB-1 mouse mesothelioma cells. Human study: 22 healthy volunteers recruited under University of Sheffield (UK) ethical approval, with full pre- and post-exercise blood data for 20. Cell lines: MSTO-211H (from the pleural effusion of a man with biphasic mesothelioma) and PANC-1 pancreatic cancer cells.
• Exposure: No asbestos exposure was studied. The exposures were exercise and immunotherapy. In the pilot, mice did different exercise activities (treadmill running and/or horizontal screen) or none. In the main pancreatic cancer and mesothelioma studies, exercising mice did both treadmill running (15 to 20 minutes per day at 12 metres per minute, at least 4 days per week; reduced to 10 minutes for the mesothelioma mice) and hanging from an inverted wire screen for 1 minute. They were given 200 ug of anti-PD1 antibody or 200 ug of an isotype control antibody. Volunteers did one session of high-intensity interval cycling. Cancer cells were cultured with serum taken before and after that exercise.
• Main results:
  • Mesothelioma mice: the exercise/anti-PD1 group had significantly more CD8+ cytotoxic T cell infiltration in tumours than the no-exercise/isotype group (p = 0.0316) and the no-exercise/anti-PD1 group (p = 0.0071).
  • Mesothelioma mice: CD8+PD1+ T cells were increased in tumours of the exercise/anti-PD1 group compared with the no-exercise/isotype group (p = 0.0138) and the no-exercise/anti-PD1 group (p = 0.0067).
  • Mesothelioma mice: tumour bioluminescence (light signal) tended to be lower in the exercising groups, but the difference was not statistically significant (p = 0.42).
  • Mesothelioma mice: flow cytometry found no statistically significant differences in immune cell subpopulations between groups. The authors noted only a trend toward fewer Tregs in the exercising groups.
  • Pancreatic cancer pilot study: mice that did treadmill running had a 92.9% reduction in liver metastatic disease compared with mice that did not run (p = 0.0087).
  • Pancreatic cancer mice (anti-PD1 study): the exercising groups had significant reductions in tumour MDSCs (73.5%, p = 0.0426) and Tregs (89.0%, p = 0.0115).
  • Pancreatic cancer mice: the largest degree of tumour necrosis was in the exercise/anti-PD1 group, compared with the no-exercise/anti-PD1 group (p = 0.0269).
  • Healthy volunteers (n = 20 with paired results, of 22 recruited): CD56+ natural killer cells in blood rose 32.6% after one session of high-intensity interval cycling (p < 0.0001, 95% CI 23.0 to 42.2%).
  • Healthy volunteers (n = 18): CD4+CD25+ cells (Tregs) fell 31.0% after exercise (p < 0.0001, 95% CI 13.7 to 48.3%).
  • Cell experiments: MSTO-211H mesothelioma cells migrated significantly less in post-exercise serum than in pre-exercise serum (p = 0.0156).
  • Cell experiments: caspase-3/7 levels (a marker of cell death by apoptosis) were higher in post-exercise serum than in pre-exercise serum, by 16.5% in PANC-1 cells (p = 0.0099) and by 6.67% in MSTO-211H cells (p = 0.0313).
• The authors' conclusion: The authors concluded that moderate-intensity exercise combined with anti-PD1 increased tumour necrosis, reduced metastatic disease and transformed the tumour microenvironment towards a 'hot' (immune-enriched) phenotype.
• Limitations the authors state:
  • All the healthy volunteers exercised regularly, so their immune changes may be smaller than those of people who do not exercise, who more closely resemble patients with advanced mesothelioma and pancreatic cancer.
  • Blood was sampled only immediately after exercise, so later changes (for example in cytokines) may have been missed.
  • Pancreatic tumours were often not visible on imaging, suggesting problems with luciferase expression or interference from the mice's black fur.
  • Further validation would be needed to show that the CD8 T cells were actually activated.
  • Functional cytotoxicity assays are needed to confirm that exercise causes immune-mediated killing of cancer cells.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Prognosis, Adenocarcinoma, Apoptosis, Necrosis.

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