Native Soluble Carcinoembryonic Antigen Is Not Involved in the Impaired Activity of CD56dim Natural Killer Cells in Malignant Pleural Effusion
Native Soluble Carcinoembryonic Antigen Is Not Involved in the Impaired Activity of CD56dim Natural Killer Cells in Malignant Pleural Effusion
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DOI：
10.1159/000345214
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发表时间：
2012-12
期刊：
影响因子：
3.7
通讯作者：
Jing Qi;Daling Li;Jing Feng;Shuo Yang;Yuan Su;M. Fang;Z. Tan;Huanzhong Shi;Xiyun Yan;F. Gong;F. Zheng
中科院分区：
文献类型：
--
作者：
Jing Qi;Daling Li;Jing Feng;Shuo Yang;Yuan Su;M. Fang;Z. Tan;Huanzhong Shi;Xiyun Yan;F. Gong;F. Zheng
背景：自然杀伤细胞（NK）是先天免疫系统的淋巴细胞，在肿瘤免疫监视中起着至关重要的作用。积累的数据表明，NK细胞在肿瘤微环境中经常表现出抑制功能。然而，其机制尚不清楚。目的：探讨肺癌患者恶性胸腔积液（MPE）对NK细胞的影响及相关机制。方法：采集肺癌患者的MPE和外周血（PB）标本。流式细胞术检测CD56dim NK细胞对PB和MPE单核细胞的细胞毒活性。结果：与配对的PB相比，MPE中总NK细胞和CD56dim NK亚群的百分比降低并伴有细胞毒性活性受损。无细胞MPE处理降低了健康供体PB中CD56dim NK细胞的比例和细胞毒活性。其抑制作用不依赖于可溶性癌胚抗原和抑制性细胞因子白介素-10和转化生长因子-β1，而依赖于分子量为100 kDa的因子。结论：这些结果表明，天然可溶性癌胚抗原不抑制NK细胞的活性，一种分子量为bbb100 kDa的未知因子在MPE中对CD56dim NK细胞的损伤起关键作用，并可能导致肿瘤进展。
Background: Natural killer (NK) cells are lymphocytes of the innate immune system that play a crucial role in tumor immune surveillance. Accumulated data indicated that NK cells in the tumor microenvironment often display a suppressed function. However, the mechanism is not clear. Objective: In this study, the effects and relative mechanisms of malignant pleural effusion (MPE) from patients with lung cancer on NK cells were researched. Methods: MPE and peripheral blood (PB) samples were collected from patients with lung cancer. The cytotoxic activity of CD56dim NK cells in PB and MPE mononuclear cells was analyzed by flow cytometry. Results: It was observed that the percentages of total NK cells and a CD56dim NK subset in MPE reduced accompanying impaired cytotoxic activity compared with that in paired PB. Cell-free MPE treatment reduced both the proportion and cytotoxic activity of CD56dim NK cells in PB from healthy donors. The suppression effects were not based on soluble carcinoembryonic antigen and the inhibitory cytokines interleukin-10 and transforming growth factor-β1, but were dependent on the factor with a molecular weight >100 kDa. Conclusions: These results demonstrated that native soluble carcinoembryonic antigen does not suppress the activity of NK cells, and an unknown factor with a molecular weight >100 kDa plays a critical role in the impairment of CD56dim NK cells in MPE, which might lead to tumor progression.