期刊
CELLS
卷 10, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cells10071702
关键词
cytotoxic lymphocytes; STAT5; pS6; inhibitory checkpoint receptor; tumor microenvironment; ectonucleotidases
类别
资金
- Sao Paulo Research Foundation-FAPESP [2018/06959-1, 2018/18047-7, 2019/25113-9, 2020/11628-4]
- CAPES
Ovarian cancer, particularly the serous histotype, is a deadly malignancy with frequent comorbidity of peritoneal ascites. Ascites from EOC patients provide a valuable sampling source for studying lymphocytes, revealing an inflammatory and immunosuppressive environment with altered signaling pathways. NK and T lymphocytes in EOC-associated ascites exhibit distinct phenotypic changes compared to blood samples, suggesting a complex interplay between the tumor microenvironment and immune cells.
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.
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