da Silva Rodrigo Fernandes, Yoshida Adriana, Cardozo Daniela Maira, Jales Rodrigo Menezes, Paust Silke, Derchain Sophie, Guimarães Fernando
Faculty of Medical Sciences, University of Campinas, 13083-887 Campinas, Brazil.
Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.
Int J Mol Sci. 2017 May 17;18(5):856. doi: 10.3390/ijms18050856.
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 ( < 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.
腹腔积液是晚期上皮性卵巢癌(EOC)患者的一个显著特征。已有报道称,EOC相关腹腔积液中存在不同的淋巴细胞亚群,这些腹腔积液也可能含有或不含有恶性细胞。本研究的目的是根据EOC相关腹腔积液中自然杀伤(NK)细胞激活受体的表达、腹腔积液中淋巴细胞亚型的含量、细胞因子谱以及EOC细胞的存在情况,分析NK细胞的功能特征。通过检测腹腔积液和血液中静息及白细胞介素(IL)-2刺激后的NK细胞中脱颗粒标志物CD107a的表达来评估NK细胞功能。在静息状态或IL-2刺激后,来自无EOC细胞腹腔积液的NK细胞脱颗粒显著高于所有其他组(P<0.05),这表明之前存在局部刺激。相比之下,IL-2处理对含有EOC细胞的腹腔积液中的NK细胞没有影响。与无EOC细胞的腹腔积液相比,含有EOC细胞的腹腔积液中调节性T细胞的数量显著更高。含有EOC细胞的腹腔积液中肿瘤坏死因子(TNF)-α水平也更高,提示与恶性肿瘤相关的炎症。总之,无EOC细胞的腹腔积液和含有EOC细胞的腹腔积液中NK细胞的功能表现不同。含有EOC细胞的腹腔积液中NK细胞对IL-2反应的受损与免疫抑制性肿瘤微环境一致。