Intracellular poly(I:C) initiated gastric adenocarcinoma cell apoptosis and subsequently ameliorated NK cell functions.
Intracellular poly(I:C) initiated gastric adenocarcinoma cell apoptosis and subsequently ameliorated NK cell functions.
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DOI：
10.1089/jir.2012.0118
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发表时间：
2014-01
期刊：
影响因子：
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通讯作者：
Jing Qu;Zhaohua Hou;Qiuju Han;Wen Jiang;Cai Zhang;Z. Tian;Jian Zhang
中科院分区：
文献类型：
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作者：
Jing Qu;Zhaohua Hou;Qiuju Han;Wen Jiang;Cai Zhang;Z. Tian;Jian Zhang
自然杀伤细胞（NK）是颗粒状淋巴细胞，在病毒感染防御和肿瘤免疫监视中发挥重要作用。然而，NK细胞的功能在癌症患者中受损。Polycytidylic acid [poly(I:C)]已被用作免疫佐剂，以改善先天和适应性免疫反应。在本研究中，胞内聚（I:C）可快速触发胃腺癌细胞凋亡。同时，poly（I:C）处理的胃腺癌细胞对NK细胞溶解的敏感性增强，MICA/B和Fas的表达升高。此外，与未经处理的肿瘤细胞上清液处理的NK细胞相比，经poly（I:C）转染的肿瘤细胞上清液显著增强了NK细胞对肿瘤细胞的细胞溶解活性，并增强了NK细胞的增殖和迁移能力。在这个过程中，NK细胞的激活受体和细胞溶解相关分子被上调。进一步研究表明，poly（I:C）转染的胃腺癌细胞产生的I型干扰素（IFN）在这一过程中发挥了重要作用。我们的研究结果表明，细胞内多聚（I:C）不仅可以触发胃腺癌细胞凋亡，还可以通过诱导胃腺癌细胞产生I型IFN来增强NK反应。这些功能使聚（I:C）成为一种很有前景的治疗胃腺癌的药物。
Natural killer (NK) cells are granular lymphocytic cells that exert essential functions in viral infection defense and tumor immune surveillance. However, the functions of NK cells were impaired in cancer patients. Polycytidylic acid [poly(I:C)] has been used as an immune adjuvant to improve innate and adaptive immune responses. In this study, intracellular poly(I:C) could trigger gastric adenocarcinoma cells apoptosis quickly. Meanwhile, the sensitivity of poly(I:C)-treated gastric adenocarcinoma cells to NK cell cytolysis was increased, concomitant with the elevated expression of MICA/B and Fas. Furthermore, the cytolytic activity of NK cells against tumor cells was augmented significantly by the supernatant from poly(I:C)-transfected tumor cells compared with NK cells treated by the supernatant from untreated tumor cells, as well as the proliferation and migration abilities of NK cells. In this process, the activating receptors and cytolysis-associated molecules of NK cells were up-regulated. Further investigation showed that type I interferon (IFN) produced by poly(I:C)-transfected gastric adenocarcinoma cells played an important role in this process. Our findings demonstrated that intracellular poly(I:C) not only triggered gastric adenocarcinoma cell apoptosis, but also enhanced NK responses via inducing type I IFN production by gastric adenocarcinoma cells. These functions make poly(I:C) a promising therapeutic medicine for gastric adenocarcinoma.