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The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and physical activity. A single event of dynamic exercise results in the substantial mobilization of leukocytes with increased functional capacities into the circulation. Chronic, or long-term, exercise leads to higher physical fitness in terms of greater cardiorespiratory function and\/or muscle strength and endurance. High aerobic capacity, as measured by maximal oxygen uptake, has been associated with the reduction of dysfunctional T cells and improvements in the abundance of some T cell populations. To be sure, however, the mechanisms of exercise-mediated immune changes are both extensive and diverse. Here, we examine the evidence and theorize how acute and chronic exercise could be used to improve responses to cancer immunotherapies including immune checkpoint inhibitors, dendritic cell vaccines, natural killer cell therapies, and adoptive T cell therapies such as chimeric antigen receptor (CAR) T cells. Although the parameters of optimal exercise to yield defined outcomes remain to be determined, the available current data provide a compelling justification for additional human studies and clinical trials investigating the adjuvant use of exercise in immuno-oncology.<\/jats:p>","DOI":"10.1136\/jitc-2020-001872","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T12:29:14Z","timestamp":1625228954000},"page":"e001872","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["Exercise and the immune system: taking steps to improve responses to cancer immunotherapy"],"prefix":"10.1136","volume":"9","author":[{"given":"Michael P","family":"Gustafson","sequence":"first","affiliation":[{"name":"Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney M","family":"Wheatley-Guy","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison C","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology, Mayo Clinic Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A","family":"Gastineau","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Katsanis","sequence":"additional","affiliation":[{"name":"Pediatrics, Immunobiology, University of Arizona Medical Center - University Campus, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Simpson","sequence":"additional","affiliation":[{"name":"Pediatrics, Immunobiology, and Nutritional Sciences, University of Arizona Medical Center - University Campus, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"2025100314024812000_9.7.e001872.1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-1426-1-7"},{"key":"2025100314024812000_9.7.e001872.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.022"},{"key":"2025100314024812000_9.7.e001872.3","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201910293","article-title":"Functional systemic CD4 immunity is required for clinical responses to PD-L1\/PD-1 blockade therapy","volume":"11","author":"Zuazo","year":"2019","journal-title":"EMBO Mol Med"},{"key":"2025100314024812000_9.7.e001872.4","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0887"},{"key":"2025100314024812000_9.7.e001872.5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ctim.2019.03.013","article-title":"The effects of physical activity on cancer prevention, treatment and prognosis: a review of the literature","volume":"44","author":"Lugo","year":"2019","journal-title":"Complement Ther Med"},{"key":"2025100314024812000_9.7.e001872.6","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1200\/JCO.19.02407","article-title":"Amount and intensity of leisure-time physical activity and lower cancer risk","volume":"38","author":"Matthews","year":"2020","journal-title":"J Clin Oncol"},{"key":"2025100314024812000_9.7.e001872.7","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2017-098391"},{"key":"2025100314024812000_9.7.e001872.8","doi-asserted-by":"publisher","DOI":"10.2307\/20056429"},{"key":"2025100314024812000_9.7.e001872.9","unstructured":"World Health Organization . 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