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The aim of this study was to investigate the immunoregulatory effects of pGSN expression on natural killer (NK) cell function in OVCA. OVCA tissues from primary surgeries underwent immunofluorescent staining of pGSN and the activated NK cell marker natural cytotoxicity triggering receptor 1 to analyze the prognostic impact of pGSN expression and activated NK cell infiltration. The immunoregulatory effects of pGSN on NK cells were assessed using apoptosis assay, cytokine secretion, immune checkpoint-receptor expression, and phosphorylation of STAT3. In OVCA tissue analyses, activated NK cell infiltration provided survival advantages to patients. However, high pGSN expression attenuated the survival benefits of activated NK cell infiltration. In the in vitro experiment, pGSN in OVCA cells induced NK cell death through cell-to-cell contact. pGSN increased T-cell immunoglobulin and mucin-domain-containing-3 expression (TIM-3) on activated NK cells. Further, it decreased interferon-\u03b3 production in activated TIM-3+ NK cells, attenuating their anti-tumor effects. Thus, increased pGSN expression suppresses the anti-tumor functions of NK cells. The study provides insights into why immunotherapy is rarely effective in patients with OVCA and suggests novel treatment strategies.<\/jats:p>","DOI":"10.3390\/cells13110905","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T06:59:04Z","timestamp":1716533944000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plasma Gelsolin Inhibits Natural Killer Cell Function and Confers Chemoresistance in Epithelial Ovarian Cancer"],"prefix":"10.3390","volume":"13","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 Medicine, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"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"},{"name":"Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Obstetrics and Gynecology, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meshach","family":"Asare-Werehene","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"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"},{"name":"Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin K.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"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"},{"name":"Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"m3773","DOI":"10.1136\/bmj.m3773","article-title":"Treatment of Epithelial Ovarian Cancer","volume":"371","author":"Kuroki","year":"2020","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.gendis.2020.11.017","article-title":"Revisiting Chemoresistance in Ovarian Cancer: Mechanism, Biomarkers, and Precision Medicine","volume":"9","author":"Guo","year":"2022","journal-title":"Genes Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrc706","article-title":"Multidrug Resistance in Cancer: Role of ATP\u2013Dependent Transporters","volume":"2","author":"Gottesman","year":"2002","journal-title":"Nat. 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