Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Ovarian Cancer-Associated Ascites Have High Proportions of Cytokine-Responsive CD56bright NK Cells

Full text
Author(s):
Tonetti, Claudia Rodrigues [1] ; de Souza-Araujo, Caroline Natania [1] ; Yoshida, Adriana [2] ; da Silva, Rodrigo Fernandes [1] ; Alves, Paulo Cesar Martins [3] ; Mazzola, Tais Nitsch [3] ; Derchain, Sophie [1, 2] ; Fernandes, Luis Gustavo Romani [1] ; Guimaraes, Fernando [1, 2]
Total Authors: 9
Affiliation:
[1] Univ Estadual Campinas, Sch Med Sci, Rua Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Womens Hosp Jose Aristodemo Pinotti, Ctr Atencao Integral Saude Mulher CAISM, Rua Alexander Fleming 101, BR-13083881 Campinas, SP - Brazil
[3] Univ Estadual Campinas, Ctr Invest Pediat, Rua Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: CELLS; v. 10, n. 7 JUL 2021.
Web of Science Citations: 0
Abstract

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 < 0.0001) higher amounts of IL-6 and IL-10 than in the patients' blood, as well as significantly (p < 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 < 0.05) pS6 phosphorylation compared with NK from blood. Additionally, in vitro treatment of lymphocytes with IL-2 or IL-15 elicited significantly (p < 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 < 0.0001) higher proportion of NK CD56bright lymphocytes than blood, which, in addition, were more responsive (p < 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. (AU)

FAPESP's process: 18/18047-7 - Cellular characterization of peripheral blood mononuclear cells and ascites cells from patients with advanced ovarian epithelial cancer
Grantee:Claudia Rodrigues Tonetti
Support type: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 19/25113-9 - Cell characterization of peripheral blood mononuclear cell samples and ascites cells of patients with advanced ovarian epithelial cancer
Grantee:Caroline Natânia de Souza Araújo
Support type: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 20/11628-4 - Cell characterization of peripheral blood mononuclear cell samples and ascites cells of patients with advanced ovarian epithelial cancer.
Grantee:Anna Carolina Emi de Lima Tanada
Support type: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 18/06959-1 - Evaluation of JAK-STAT5 and mTOR-S6 signaling pathways in functional modulation of natural killer (NK) cells from patients with epithelial ovarian cancer
Grantee:Fernando Guimarães
Support type: Regular Research Grants