{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:35:25Z","timestamp":1787783725841,"version":"build-2784847793"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the present study, we report the analysis of NK cells derived from patients suffering from a rare ovarian cancer histotype of clear cell carcinoma (OCCC) resistant to conventional chemotherapies. We analyzed the phenotype of NK cells derived from peripheral blood (PB) and peritoneal fluid (PF) and evaluated cytotoxic interactions between NK cells and autologous tumor cells (ATC) derived from patients. We provided evidence of impaired degranulation capacity of NK cells derived from patients\u2019 PF in the presence of ATC. Analyzing tumor cell ligands recognized by NK cell receptors, we found that ATC are characterized by an HLA class I+ phenotype (although the level of HLA-I expression varies among all patients) and by a heterogeneous expression of ligands for activating NK receptors (from normal to decreased expression of some markers). Furthermore, we observed a down-regulation of crucial NK cell activating receptors, primarily DNAX Accessory Molecule-1 (DNAM-1), on tumor-associated NK cells. Based on these results, we propose that this severe lysis defect may be due to both negative interactions between HLA-I-specific inhibitory NK cell receptors\/HLA-I molecules and to defective interactions between activating NK receptors and cognate ligands. In conclusion, for the first time, the phenotypic and functional properties of tumor-associated NK cells and their ATC derived from PF of patients with advanced stage of OCCC were characterized. Taken together results indicate altered interactions between NK cells and ATC and shed light on the aggressive mechanisms of this cancer histotype. Further studies on this rare tumor will be helpful to improve and define more effective therapies.<\/jats:p>","DOI":"10.1002\/jlb.5ma0720-295r","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T04:49:53Z","timestamp":1597380593000},"page":"1425-1434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural killer cell impairment in ovarian clear cell carcinoma"],"prefix":"10.1093","volume":"108","author":[{"given":"Ornella","family":"Patrizi","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Rampinelli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Spedali Civili di Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Coltrini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Carlomagno","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sivori","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Pascale","sequence":"additional","affiliation":[{"name":"Innate Pharma SA , Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-7566","authenticated-orcid":true,"given":"Emanuela","family":"Marcenaro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genoa , Genoa , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Parolini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Tabellini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia , Brescia , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"2023032108080209100_jlb10767-cit-0001","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/CCO.0b013e328363e0c7","article-title":"Clear cell cancer of the ovary","volume":"25","author":"Penson","year":"2013","journal-title":"Curr Opin Oncol"},{"issue":"Suppl 1","key":"2023032108080209100_jlb10767-cit-0002","doi-asserted-by":"crossref","first-page":"i50","DOI":"10.1093\/annonc\/mdw086","article-title":"Clear-cell carcinoma of the ovary","volume":"27","author":"Fujiwara","year":"2016","journal-title":"Ann Oncol"},{"key":"2023032108080209100_jlb10767-cit-0003","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.ygyno.2012.04.021","article-title":"Clear cell carcinoma of the ovary: a review of the literature","volume":"126","author":"del Carmen","year":"2012","journal-title":"Gynecol Oncol"},{"key":"2023032108080209100_jlb10767-cit-0004","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.humpath.2009.01.002","article-title":"Hobnail-like cells in serous borderline tumor do not represent concomitant incipient clear cell neoplasms","volume":"40","author":"Ohishi","year":"2009","journal-title":"Hum Pathol"},{"key":"2023032108080209100_jlb10767-cit-0005","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1198687","article-title":"Innate or adaptive immunity? 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