{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:59:55Z","timestamp":1790125195415,"version":"4.0.1"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT169175"],"award-info":[{"award-number":["PJT169175"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"publisher","award":["23727"],"award-info":[{"award-number":["23727"]}],"id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cachexia is a major cause of death in cancer and leads to wasting of cardiac and skeletal muscle, as well as adipose tissue. Various cellular and soluble mediators have been postulated in driving cachexia; however, the specific mechanisms behind this muscle wasting remain poorly understood. In this study, we found polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to be critical for the development of cancer-associated cachexia. Significant expansion of PMN-MDSCs was observed in the cardiac and skeletal muscles of cachectic murine models. Importantly, the depletion of this cell subset, using depleting anti-Ly6G Abs, attenuated this cachectic phenotype. To elucidate the mechanistic involvement of PMN-MDSCs in cachexia, we examined major mediators, that is, IL-6, TNF-\u03b1, and arginase 1. By employing a PMN-MDSC\u2013specific Cre-recombinase mouse model, we showed that PMN-MDSCs were not maintained by IL-6 signaling. In addition, PMN-MDSC\u2013mediated cardiac and skeletal muscle loss was not abrogated by deficiency in TNF-\u03b1 or arginase 1. Alternatively, we found PMN-MDSCs to be critical producers of activin A in cachexia, which was noticeably elevated in cachectic murine serum. Moreover, inhibition of the activin A signaling pathway completely protected against cardiac and skeletal muscle loss. Collectively, we demonstrate that PMN-MDSCs are active producers of activin A, which in turn induces cachectic muscle loss. Targeting this immune\/hormonal axis will allow the development of novel therapeutic interventions for patients afflicted with this debilitating syndrome.<\/jats:p>","DOI":"10.4049\/jimmunol.2200064","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T10:46:54Z","timestamp":1686307614000},"page":"497-507","source":"Crossref","is-referenced-by-count":18,"title":["Activin A\u2013Expressing Polymorphonuclear Myeloid-Derived Suppressor Cells Infiltrate Skeletal and Cardiac Muscle and Promote Cancer Cachexia"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9041-4677","authenticated-orcid":false,"given":"Kasia","family":"Dzierlega","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Alberta 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Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Alberta ,","place":["Canada"]},{"name":"Department of Oncology, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-5233","authenticated-orcid":false,"given":"Sue","family":"Tsai","sequence":"additional","affiliation":[{"name":"Cancer Research Institute of Northern Alberta, University of Alberta , Edmonton, Alberta ,","place":["Canada"]},{"name":"Li Ka Shing Institute of Virology, University of Alberta , Edmonton, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8702-0957","authenticated-orcid":false,"given":"Daniel A","family":"Winer","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Ontario ,","place":["Canada"]},{"name":"Department of Pathology, University Health Network , Toronto, Ontario ,","place":["Canada"]},{"name":"Buck Institute for Research on Aging , Novato, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-4971","authenticated-orcid":false,"given":"Xavier","family":"Clemente-Casares","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Alberta ,","place":["Canada"]},{"name":"Cancer Research Institute of Northern Alberta, University of Alberta , Edmonton, Alberta ,","place":["Canada"]},{"name":"Li Ka Shing Institute of Virology, 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