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

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]}

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

• 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 Opportunities: 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 Opportunities: 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 Opportunities: 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 Opportunities: Regular Research Grants