{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:55:42Z","timestamp":1790780142369,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Claudia R Tonetti's scholarship"],"award-info":[{"award-number":["Claudia R Tonetti's scholarship"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/06959-1, 2018\/18047-7, 2019\/25113-9 and 2020\/11628-4"],"award-info":[{"award-number":["2018\/06959-1, 2018\/18047-7, 2019\/25113-9 and 2020\/11628-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ovarian cancer is the most lethal gynecological malignancy, with serous histotype as the most prevalent epithelial ovarian cancer (EOC). Peritoneal ascites is a frequent comorbidity in advanced EOC. EOC-associated ascites provide a reliable sampling source for studying lymphocytes directly from tumor environment. Herein, we carried out flow cytometry-based analysis to readdress issues on NK and T lymphocyte subsets in women with advanced EOC, additionally evaluating phenotypic modulation of their intracellular pathways involved in interleukin (IL)-2 and IL-15 signaling. Results depicted ascites as an inflammatory and immunosuppressive environment, presenting significantly (p &lt; 0.0001) higher amounts of IL-6 and IL-10 than in the patients\u2019 blood, as well as significantly (p &lt; 0.05) increased expression of checkpoint inhibitory receptors (programmed death protein-1, PD-1) and ectonucleotidase (CD39) on T lymphocytes. However, NK lymphocytes from EOC-associated ascites showed higher (p &lt; 0.05) pS6 phosphorylation compared with NK from blood. Additionally, in vitro treatment of lymphocytes with IL-2 or IL-15 elicited significantly (p &lt; 0.001) phosphorylation of the STAT5 protein in NK, CD3 and CD8 lymphocytes, both from blood and ascites. EOC-associated ascites had a significantly (p &lt; 0.0001) higher proportion of NK CD56bright lymphocytes than blood, which, in addition, were more responsive (p &lt; 0.05) to stimulation by IL-2 than CD56dim NK. EOC-associated ascites allow studies on lymphocyte phenotype modulation in the tumor environment, where inflammatory profile contrasts with the presence of immunosuppressive elements and development of cellular self-regulating mechanisms.<\/jats:p>","DOI":"10.3390\/cells10071702","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T02:59:47Z","timestamp":1625540387000},"page":"1702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Ovarian Cancer-Associated Ascites Have High Proportions of Cytokine-Responsive CD56bright NK Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Cl\u00e1udia Rodrigues","family":"Tonetti","sequence":"first","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Nat\u00e2nia","family":"de Souza-Ara\u00fajo","sequence":"additional","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Centro de Aten\u00e7\u00e3o Integral \u00e0 Sa\u00fade da Mulher (CAISM), Women\u2019s Hospital Jos\u00e9 Aristodemo Pinotti, University of Campinas, Rua Alexander Fleming-101, Campinas CEP 13083-881, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-1109","authenticated-orcid":false,"given":"Rodrigo Fernandes","family":"da Silva","sequence":"additional","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo C\u00e9sar Martins","family":"Alves","sequence":"additional","affiliation":[{"name":"Center for Investigation in Pediatrics, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta\u00eds Nitsch","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Center for Investigation in Pediatrics, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Derchain","sequence":"additional","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"},{"name":"Centro de Aten\u00e7\u00e3o Integral \u00e0 Sa\u00fade da Mulher (CAISM), Women\u2019s Hospital Jos\u00e9 Aristodemo Pinotti, University of Campinas, Rua Alexander Fleming-101, Campinas CEP 13083-881, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds Gustavo Romani","family":"Fernandes","sequence":"additional","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-972X","authenticated-orcid":false,"given":"Fernando","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"School of Medicine Sciences, University of Campinas, Rua Tess\u00e1lia Vieira de Camargo-126, Campinas CEP 13083-887, SP, Brazil"},{"name":"Centro de Aten\u00e7\u00e3o Integral \u00e0 Sa\u00fade da Mulher (CAISM), Women\u2019s Hospital Jos\u00e9 Aristodemo Pinotti, University of Campinas, Rua Alexander Fleming-101, Campinas CEP 13083-881, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nrc1611","article-title":"Ovarian Cancer Metastasis: Integrating insights from disparate model organisms","volume":"5","author":"Naora","year":"2005","journal-title":"Nat. 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