{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:21:49Z","timestamp":1787862109916,"version":"build-2784847793"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mackenzie Charitable Foundation"},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"crossref"}]},{"name":"McGee Fellowship Fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving cancer outcomes. We conducted an exploratory study to investigate how tumor burden and cancer immunotherapy treatment (anti-PD-1) modify the skeletal muscle mitochondrial response to exercise training in mice with transplantable tumors (B16-F10 melanoma and EO771 breast cancer). Mice remained sedentary or were provided with running wheels for ~19 days immediately following tumor implant while receiving no treatment (Untreated), isotype control antibody (IgG2a) or anti-PD-1. Exercise and anti-PD-1 did not alter the growth rate of either tumor type, either alone or in combination therapy. Untreated mice with B16-F10 tumors showed increases in most measured markers of skeletal muscle mitochondrial content following exercise training, as did anti-PD-1-treated mice, suggesting increased mitochondrial content following exercise training in these groups. However, mice with B16-F10 tumors receiving the isotype control antibody did not exhibit increased skeletal muscle mitochondrial content following exercise. In untreated mice with EO771 tumors, only citrate synthase activity and complex IV activity were increased following exercise. In contrast, IgG2a and anti-PD-1-treated groups both showed robust increases in most measured markers following exercise. These results indicate that in mice with B16-F10 tumors, IgG2a administration prevents exercise adaptation of skeletal muscle mitochondria, but adaptation remains intact in mice receiving anti-PD-1. In mice with EO771 tumors, both IgG2a and anti-PD-1-treated mice show robust skeletal muscle mitochondrial exercise responses, while untreated mice do not. Taken together, we postulate that immune modulation may enhance skeletal muscle mitochondrial response to exercise in tumor-bearing mice, and suggest this as an exciting new avenue for future research in exercise oncology.<\/jats:p>","DOI":"10.1371\/journal.pone.0258831","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T22:21:17Z","timestamp":1634854877000},"page":"e0258831","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-5282","authenticated-orcid":true,"given":"Linda A.","family":"Buss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Hock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy L.","family":"Merry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel D.","family":"Ang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"Currie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabi U.","family":"Dachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"pone.0258831.ref001","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/B978-0-12-386456-7.01913-4","volume-title":"Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms.","author":"B Reeves","year":"2014"},{"issue":"6","key":"pone.0258831.ref002","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/jcsm.12232","article-title":"Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice","volume":"8","author":"JL Brown","year":"2017","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"1","key":"pone.0258831.ref003","doi-asserted-by":"crossref","DOI":"10.1038\/s41523-020-0162-2","article-title":"Skeletal muscle reprogramming by breast cancer regardless of treatment history or tumor molecular subtype","volume":"6","author":"HE Wilson","year":"2020","journal-title":"npj Breast Cancer"},{"issue":"11","key":"pone.0258831.ref004","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1249\/01.mss.0000233799.62153.19","article-title":"Training for Endurance and Strength: Lessons from Cell Signaling","volume":"38","author":"K Baar","year":"2006","journal-title":"Med Sci Sport Exerc"},{"key":"pone.0258831.ref005","first-page":"1","article-title":"Skeletal muscle mitochondrial remodeling in exercise and diseases","author":"Z Gan","year":"2018","journal-title":"Cell Res"},{"issue":"2","key":"pone.0258831.ref006","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s13539-011-0047-1","article-title":"The effect of exercise on IL-6-induced cachexia in the ApcMin\/+ mouse","volume":"3","author":"MJ Puppa","year":"2012","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"pone.0258831.ref007","article-title":"Moderate exercise in mice improves cancer plus chemotherapy-induced muscle wasting and mitochondrial alterations","author":"R Ballar\u00f2","year":"2019","journal-title":"FASEB J"},{"issue":"6","key":"pone.0258831.ref008","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1001\/jamainternmed.2016.1548","article-title":"Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44","volume":"176","author":"SC Moore","year":"2016","journal-title":"Million Adults. 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