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Int. J. Mol. Sci. 2017, 18(5), 856; doi:10.3390/ijms18050856

Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients

1
Faculty of Medical Sciences, University of Campinas, 13083-887 Campinas, Brazil
2
Center for Human Immunobiology, Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX 77030, USA
3
Women´s Hospital “Professor Doutor José Aristodemo Pinotti”–Centro de Atenção Integral à Saúde da Mulher (CAISM), University of Campinas, 13083-881 Campinas, Brazil
*
Author to whom correspondence should be addressed.
Academic Editors: Nicholas Huntington and Sam Kung
Received: 23 February 2017 / Revised: 10 April 2017 / Accepted: 13 April 2017 / Published: 17 May 2017
(This article belongs to the Special Issue Natural Killer (NK) Cells)
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Abstract

Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites’ contents of lymphocyte subtypes, cytokine profile and presence of EOC cells. NK cell function was evaluated by the expression of the degranulation marker CD107a in resting and interleukin (IL)-2 stimulated NK cells from ascites and blood. Degranulation of NK cells from EOC cell-free ascites was significantly (p < 0.05) higher than all the other groups, either in their resting state or after IL-2 stimulation, suggesting a previous local stimulation. In contrast, treatment with IL-2 had no effect on NK cells from ascites with EOC cells. The amount of regulatory T cells was significantly higher in ascites with EOC cells compared to EOC cell-free ascites. Ascites with EOC cells also had higher levels of tumor necrosis factor (TNF)-α, suggesting inflammation related to the malignancy. In conclusion, the functional performance of NK cells was distinct between EOC cell-free ascites and ascites with EOC cells. The impairment of NK cell response to IL-2 in ascites with EOC cells was consistent with an immunosuppressive tumor microenvironment. View Full-Text
Keywords: tumor microenvironment; regulatory T-lymphocytes; natural killer activating receptors; CD107a tumor microenvironment; regulatory T-lymphocytes; natural killer activating receptors; CD107a
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MDPI and ACS Style

da Silva, R.F.; Yoshida, A.; Cardozo, D.M.; Jales, R.M.; Paust, S.; Derchain, S.; Guimarães, F. Natural Killer Cells Response to IL-2 Stimulation Is Distinct between Ascites with the Presence or Absence of Malignant Cells in Ovarian Cancer Patients. Int. J. Mol. Sci. 2017, 18, 856.

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