{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:40Z","timestamp":1785407560019,"version":"3.56.0"},"reference-count":79,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010 168949"],"award-info":[{"award-number":["PJT\u2010 168949"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PJT\u2010 168949"],"award-info":[{"award-number":["PJT\u2010 168949"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K12526"],"award-info":[{"award-number":["24K12526"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24K12526"],"award-info":[{"award-number":["24K12526"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Natural killer (NK) cells are key mediators of antitumor immunity; however, NK cell dysfunction in epithelial ovarian cancer should be considered not as a uniform defect, but rather as compartment-specific states that differ across the blood, ascites, primary tumor, and metastatic sites according to their local cellular interactions, soluble factors, and metabolic constraints. Peripheral blood provides an accessible systemic reference and may support immune monitoring. However, it does not fully reflect NK cell states in local or distant disease compartments. In ascites, cytokine-responsive and partially recoverable NK cell populations coexist with soluble, biochemical, and metabolic suppressive signals. In primary tumors, NK cells often acquire tissue-adapted suppressive phenotypes, characterized by altered activating receptors, increased inhibitory checkpoints, and reduced cytotoxic effector function. In metastatic lesions, NK cells appear to share suppressive phenotypes with primary tumors, although these phenotypes may be reinforced within metastatic niches through coordinated inhibitory receptor\u2013ligand interactions. The above compartment-specific states imply that NK cell-targeted therapy for ovarian cancer should not rely on a unilateral strategy. Instead, therapeutic design may need to be multifaceted but coordinated, combining cytokine-based activation, adoptive NK cell transfer, checkpoint blockade, local delivery, and antigen-directed chimeric antigen receptor NK cell approaches according to the dominant biology of each compartment. Paired multi-compartment profiling and longitudinal functional assessment will be essential for biomarker development and compartment-guided treatment design.<\/jats:p>","DOI":"10.3390\/cells15141243","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Killer Cell Plasticity in Epithelial Ovarian Cancer and Their Therapeutic Implications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-7584","authenticated-orcid":false,"given":"Toshimichi","family":"Onuma","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meshach","family":"Asare-Werehene","sequence":"additional","affiliation":[{"name":"Inflammation and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Lifelabs Medical Laboratory Services, Toronto, ON M9W 6J6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-9579","authenticated-orcid":false,"given":"Makoto","family":"Orisaka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin K.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Inflammation and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine & Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"Department of Cellular and Molecular Medicine & The Centre for Infection, Immunity and Inflammation (CI3), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mo, L., Pospichalova, V., Huang, Z., Murphy, S.K., Payne, S., Wang, F., Kennedy, M., Cianciolo, G.J., Bryja, V., and Pizzo, S.V. 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