Physical Activity as a Modulator of Cancer Immunotherapy Efficacy: A Narrative Review of Experimental and Clinical Evidence
DOI:
https://doi.org/10.12775/QS.2026.60.72895Keywords
physical activity, exercise; cancer immunotherapy, immune checkpoint inhibitors, tumor microenvironment, exercise oncology, myokinesAbstract
Background. Cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs), has transformed oncology. However, many patients show limited response or develop resistance. Physical activity is known to modulate immune function and the tumor microenvironment, suggesting it could serve as a valuable adjunct to immunotherapy.
Aim. This narrative review aims to synthesize current evidence on the influence of physical activity and structured exercise on the efficacy of cancer immunotherapy.
Material and methods. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus databases (mainly 2018-2026). Relevant preclinical, observational, and clinical studies linking physical activity/exercise with immunotherapy outcomes were included.
Results. Preclinical studies show that exercise enhances the anti-tumor effects of ICIs by increasing CD8+ T cell and NK cell infiltration, reducing immunosuppressive cells, decreasing tumor hypoxia, and releasing immunostimulatory myokines. Emerging clinical data indicate that higher physical activity levels are associated with better response rates and improved survival in patients on immunotherapy. Several randomized trials are ongoing.
Conclusions. Current evidence supports the potential of physical activity as a safe and accessible adjunct to cancer immunotherapy. Large-scale randomized controlled trials are needed to determine optimal exercise protocols and confirm clinical benefits.
References
Al-Mhanna, S., Ghazali, W., Mohamed, M., Rabaan, A., Santali, E., Alestad, J., Santali, E., Arshad, S., Ahmed, N., & Afolabi, H (2022). Effectiveness of physical activity on immunity markers and quality of life in cancer patient: a systematic review. PeerJ, 10. https://doi.org/10.7717/peerj.13664
Ashcraft, K., Warner, A., Jones, L., & Dewhirst, M. (2019). Exercise as Adjunct Therapy in Cancer.. Seminars in radiation oncology, 29 1, 16-24 https://doi.org/10.1016/j.semradonc.2018.10.001
Bagchi, S., Yuan, R., & Engleman, E. (2020). Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance.. Annual review of pathology. https://doi.org/10.1146/annurev-pathol-042020-042741
Bettariga, F., Taaffe, D., Galvão, D., Lopez, P., Bishop, C., Markarian, A., Natalucci, V., Kim, J., & Newton, R. (2024). Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis. Journal of Sport and Health Science, 13, 764 -779. https://doi.org/10.1016/j.jshs.2024.04.005.
Brummer, C., Pukrop, T., Wiskemann, J., Bruss, C., Ugele, I., & Renner, K. (2023). Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?. Cancers, 15. https://doi.org/10.3390/cancers15184668.
Buzaglo, G., Telles, G., Araújo, R., S, G., Ruberti, O., Ferreira, M., Derchain, S., Vechin, F., & Conceição, M. (2024). The Therapeutic Potential of Physical Exercise in Cancer: The Role of Chemokines. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms252413740.
Casciano, F., Caruso, L., Zauli, E., Gonelli, A., Zauli, G., & Vaccarezza, M. (2024). Emerging Mechanisms of Physical Exercise Benefits in Adjuvant and Neoadjuvant Cancer Immunotherapy. Biomedicines, 12. https://doi.org/10.3390/biomedicines12112528.
Chen, M., Raj, R., Fox, L., Moss, C., George, G., Karagiannis, S., Enting, D., Joseph, M., Peat, N., Russell, B., & Van Hemelrijck, M. (2021). Is there a role for physical activity when treating patients with cancer with immune checkpoint inhibitors? Protocol for a scoping review. BMJ Open, 11. https://doi.org/10.1136/bmjopen-2020-046052.
Dias-Da-Silva, G., Panissa, V., Derchain, S., Ferreira, M., Telles, G., Buzaglo, G., Araújo, R., Vechin, F., & Conceição, M. (2024). High-Intensity Interval Training for Cancer Patients: A Review of Key Considerations for Exercise Prescription. Sports Medicine, 55, 619 -639. https://doi.org/10.1007/s40279-024-02145-7
Fiuza-Luces, C., Valenzuela, P., Gálvez, B., Ramírez, M., López-Soto, A., Simpson, R., & Lucia, A. (2023). The effect of physical exercise on anticancer immunity. Nature Reviews Immunology, 24, 282-293. https://doi.org/10.1038/s41577-023-00943-0
Gebhardt, K., & Krüger, K. (2022). Supporting tumor therapy by exercise: boosting T cell immunity by myokines. Signal Transduction and Targeted Therapy, 7. https://doi.org/10.1038/s41392-022-01116-6.
Gomes-Santos, I., Amoozgar, Z., Kumar, A., Ho, W., Roh, K., Talele, N., Curtis, H., Kawaguchi, K., Jain, R., & Fukumura, D. (2021). Exercise Training Improves Tumor Control by Increasing CD8+ T-cell Infiltration via CXCR3 Signaling and Sensitizes Breast Cancer to Immune Checkpoint Blockade. Cancer Immunology Research, 9, 765 -778. https://doi.org/10.1158/2326-6066.cir-20-0499.
Gouez, M., Rébillard, A., Thomas, A., Beaumel, S., Matera, E., Gouraud, E., Orfila, L., Martin, B., Pérol, O., Chaveroux, C., Chirico, E., Dumontet, C., Fervers, B., & Pialoux, V. (2024). Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1368550.
Gundakaram, S., Sirigireddy, S., McDonald, A., King, E., & Goparaju, P. (2025). Evaluating the role of exercise in modulating immunity and immunotherapy outcomes in cancer: A systematic review.. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2025.43.16_suppl.2646
Gustafson, M., Wheatley-Guy, C., Rosenthal, A., Gastineau, D., Katsanis, E., Johnson, B., & Simpson, R. (2021). Exercise and the immune system: taking steps to improve responses to cancer immunotherapy. Journal for Immunotherapy of Cancer, 9. https://doi.org/10.1136/jitc-2020-001872.
Hapuarachi, B., Danson, S., Wadsley, J., & Muthana, M. (2023). Exercise to transform tumours from cold to hot and improve immunotherapy responsiveness. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1335256.
Hayes, S., Newton, R., Spence, R., & Galvão, D. (2019). The Exercise and Sports Science Australia position statement: Exercise medicine in cancer management.. Journal of science and medicine in sport. https://doi.org/10.1016/j.jsams.2019.05.003
Hossain, M. (2024). A comprehensive review of immune checkpoint inhibitors for cancer treatment.. International immunopharmacology, 143 Pt 2, 113365. https://doi.org/10.1016/j.intimp.2024.113365
Huang, Y., , N., & Ren, W. (2025). Investigating the therapeutic efficacy of physical exercise on tumor immunity in a mouse model of malignant colon cancer. Immunopharmacology and Immunotoxicology, 48, 34 -42. https://doi.org/10.1080/08923973.2025.2600941.
Idorn, M., & Straten, T. (2017). Exercise and cancer: from “healthy” to “therapeutic”?. Cancer Immunology, Immunotherapy : CII, 66, 667 -671. https://doi.org/10.1007/s00262-017-1985-z
Invernizzi, M., Lippi, L., Folli, A., Turco, A., Zattoni, L., Maconi, A., De Sire, A., & Fusco, N. (2022). Integrating molecular biomarkers in breast cancer rehabilitation. What is the current evidence? A systematic review of randomized controlled trials. Frontiers in Molecular Biosciences, 9. https://doi.org/10.3389/fmolb.2022.930361
Koper, M., & Bochenek, O. (2024). From Diagnosis to Recovery: The Life-Changing Benefits of Exercise for Cancer Patients. Quality in Sport, 20, 54212. https://doi.org/10.12775/QS.2024.20.54212
Lavín-Pérez, A., Collado-Mateo, D., Abbasi, S., Ferreira-Júnior, J., & Hekmatikar, A. (2023). Effects of exercise on immune cells with tumor-specific activity in breast cancer patients and survivors: a systematic review and meta-analysis. Supportive Care in Cancer, 31. https://doi.org/10.1007/s00520-023-07968-0
Liu, J., Liu, W., Wan, Y., & Mao, W. (2024). Crosstalk between Exercise and Immunotherapy: Current Understanding and Future Directions. Research, 7. https://doi.org/10.34133/research.0360
Loo, K., Lavery, J., Palmer, J., Guo, W., Underwood, W., Moskowitz, C., Jones, L., & Betof, A. (2025). Association between exercise and clinical outcomes in patients treated with immunotherapy for solid tumors. Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1694045.
Luo, Z., Mei, J., Wang, X., Wang, R., He, Z., Geffen, Y., Sun, X., Zhang, X., Xu, J., Wan, R., Feng, X., Jiao, C., Su, X., Sun, J., Chen, S., Chen, J., Mao, W., Yang, Y., & Sun, Y. (2024). Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment.. Cell reports, 43 9, 114697 . https://doi.org/10.1016/j.celrep.2024.114697.
Lyu, D. (2024). Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review. Frontiers in Physiology, 14. https://doi.org/10.3389/fphys.2023.1292580.
Oliveira, E., Correia, I., Bernardino, A., Hetherington-Rauth, M., Boavida, S., Sardinha, L., & Magalhães, J. (2025). Effect of Exercise on Immune System Markers in Cancer Patients and Survivors: A Systematic Review Journal of sports science & medicine, 24 3, 645-665. https://doi.org/10.52082/jssm.2025.645
Olofsson, H., Mikkelsen, M., Ragle, A., Christiansen, A., Olsen, A., Heide-Ottosen, L., Horsted, C., Pedersen, C., Engell-Noerregaard, L., Lorentzen, T., Persson, G., Vinther, A., Nielsen, D., & Straten, T. (2022). High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)-a randomized controlled trial. BMC Cancer, 22. https://doi.org/10.1186/s12885-022-09349-y.
Orange, S., Leslie, J., Ross, M., Mann, D., & Wackerhage, H. (2023). The exercise IL-6 enigma in cancer.. Trends in endocrinology and metabolism: TEM. https://doi.org/10.1016/j.tem.2023.08.001.
Sitlinger, A., Brander, D., & Bartlett, D. (2020). Impact of exercise on the immune system and outcomes in hematologic malignancies.. Blood advances, 4 8, 1801-1811. https://doi.org/10.1182/bloodadvances.2019001317
Smuszkiewicz-Różański, P., Różańska-Smuszkiewicz, G., Kmiotek, W., Ragan, D., Oronowicz, R., Staszczak, P., Jaworska, B., Długosz, J., Bara, M., & Jama, G. (2024). Holistic approach to oncology patients with a special focus on physical activity – a literature review. Quality in Sport, 20, 53434. https://doi.org/10.12775/QS.2024.20.53434
Spiliopoulou, P., Gavriatopoulou, M., Kastritis, E., Dimopoulos, M., & Terzis, G. (2021). Exercise-Induced Changes in Tumor Growth via Tumor Immunity. Sports, 9. https://doi.org/10.3390/sports9040046.
Straten, P. (2025). The exercise of mobilizing the immune system in cancer patients. South East European Journal of Immunology. https://doi.org/10.3889/seejim.2025.6114.
Wennerberg, E., Lhuillier, C., Rybstein, M., Dannenberg, K., Rudqvist, N., Koelwyn, G., Jones, L., & Demaria, S. (2020). Exercise reduces immune suppression and breast cancer progression in a preclinical model. Oncotarget, 11, 452 -461. https://doi.org/10.18632/oncotarget.27464.
Yin, Q., Wu, L., Han, L., Zheng, X., Tong, R., Li, L., Bai, L., & Bian, Y. (2023). Immune-related adverse events of immune checkpoint inhibitors: a review. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1167975
Yu, X., Pei, W., Li, B., Sun, S., Li, W., & Wu, Q. (2025). Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy. International Journal of Biological Sciences, 21, 910 -939. https://doi.org/10.7150/ijbs.100948
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Copyright (c) 2026 Paulina Julia Jainta, Anna Maria Wicher, Nikola Podyma, Izabela Kempska, Paweł Kamil Harmansa, Julita Zofia Gwóźdź, Ziemowit Szczygłowski, Alina Torbicka, Patryk Zieleziński, Paulina Anna Fryszkiewicz
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