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

Sep 22, 2026

Exercise modulates the immune system and may strengthen anti-cancer activity, potentially synergizing with cancer immunotherapy. Tumours with low immune infiltration (“cold” tumours) often respond poorly to immunotherapy and have worse outcomes. Using mouse pancreatic cancer and mesothelioma models, the study evaluates aerobic and resistance exercise paired with anti-PD-1, mapping changes in tumour immune populations and tumour growth, metastasis, and microenvironment remodeling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

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Abstract

Background

Methods

Results

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Introduction

Article Exercise Boosts the Immune System and Enhances Immunotherapy Responses in Pancreatic Cancer and Mesothelioma Brindley Hapuarachi 1,2, *, Sarah Danson 1,2, Jonathan Wadsley 2, Hannah Brown 1, Phoebe Southam 1 and Munitta Muthana 1, * Academic Editors: Dorota Kostrzewa-Nowak, Robert Nowak, Michał Sławi ´nski and Patrizia Proia Received: 13 February 2026 Revised: 17 March 2026 Accepted: 18 March 2026 Published: 25 March 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Division of Clinical Medicine, University of Sheffield, Sheffield S10 2TN, UK; s.danson@sheffield.ac.uk (S.D.); [hannahbrown1306@gmail.com](hannahbrown1306@gmail.com) (H.B.); [psoutham1@sheffield.ac.uk](psoutham1@sheffield.ac.uk) (P.S.) 2 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; jonathan.wadsley1@nhs.net * Correspondence: sbhapuarachchi1@sheffield.ac.uk (B.H.); m.muthana@sheffield.ac.uk (M.M.) 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, exerciseconditioned 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. Keywords: exercise; immunotherapy; immunology; tumour microenvironment 1. Introduction Aerobic exercise has known benefits for physical and mental health in both the general population and in patients with cancer. In cancers such as breast and colorectal cancer, exercise has been shown to reduce the risk of cancer recurrence following curative surgery an

FAQs

How does the study connect exercise with immunotherapy benefits in pancreatic cancer and mesothelioma?

It tests exercise combined with anti-PD-1 to determine whether exercise can reshape the tumour immune landscape and improve responses in poorly immunogenic (“cold”) cancers.

What models and interventions were used to evaluate the effect of exercise?

C57BL/6 mice received orthotopic PANC02 pancreatic cancer cells and BALB/c mice received intraperitoneal AB-1 mesothelioma cells, followed by groups receiving exercise with anti-PD-1, exercise with isotype, no exercise with anti-PD-1, or no exercise with isotype.

What immune and tumour changes were observed after combining exercise with immunotherapy?

The combination increased tumour necrosis and reduced metastatic potential, enhanced cytotoxic CD8+ T cell infiltration, upregulated PD-1, and reduced myeloid-derived suppressor cells and regulatory T cells.

Sep 22, 2026

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