{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:32Z","timestamp":1792789172012,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Major Science and Technology Projects of China","award":["2023ZD0502002"],"award-info":[{"award-number":["2023ZD0502002"]}]},{"name":"National Natural Science Foundation of China","award":["82573497"],"award-info":[{"award-number":["82573497"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"award":["82573497"],"award-info":[{"award-number":["82573497"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Science and Technology Support Program of Sichuan Province","award":["2025NSFSC0566"],"award-info":[{"award-number":["2025NSFSC0566"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Erythropoietin (EPO) is a hypoxia-responsive glycoprotein hormone that sustains erythroid progenitor survival through the erythropoietin receptor (EPOR). Beyond erythropoiesis, emerging evidence places the EPO\/EPOR axis at the interface of tumor adaptation, stromal remodeling, and immune tolerance. Interpretation has been complicated by nonspecific antibodies, low receptor abundance, and failure to distinguish EPOR transcripts or intracellular proteins from ligand-accessible, functional cell-surface receptors. Recent mechanistic studies have established immunoregulatory roles: tumor-derived EPO reprograms EPOR-positive macrophages through nuclear factor erythroid 2-related factor 2 (NRF2)-dependent heme depletion, whereas EPOR signaling in conventional type 1 dendritic cells promotes tolerance and restrains antitumor T-cell priming. EPO-driven expansion of CD71-positive nucleated erythroid cells provides an additional systemic suppressive route. Evidence for direct effects on tumor cell survival, angiogenesis, and treatment resistance is more heterogeneous and must be interpreted in light of receptor validation, model context, and exposure conditions. This critical narrative review introduces operational evidence categories, distinguishes exploratory tissue screening from causal validation, and proposes a scalable experimental framework with minimum, enhanced, and gold-standard levels. Clinically, erythropoiesis-stimulating agents remain supportive care agents, not anticancer therapies; their use is restricted by thromboembolic risk and historical survival concerns. Translational development should prioritize practical biomarker panels and tumor- or cell-selective interventions that preserve erythropoietic safety.<\/jats:p>","DOI":"10.3390\/cancers18183011","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"3011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Erythropoietin in Tumor Immunity: Mechanistic Evidence, Clinical Cautions, and Translational Opportunities"],"prefix":"10.3390","volume":"18","author":[{"given":"Tongsheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Liver Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Liver Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-3766","authenticated-orcid":false,"given":"Tian","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Liver Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a011619","DOI":"10.1101\/cshperspect.a011619","article-title":"Erythropoietin","volume":"3","author":"Bunn","year":"2013","journal-title":"Cold Spring Harb. 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