Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Institute of Immunopharmacology and Immunotherapy, Shandong University , Jinan, China .
J Interferon Cytokine Res. 2014 Jan;34(1):52-9. doi: 10.1089/jir.2012.0118. Epub 2013 Sep 13.
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.
自然杀伤 (NK) 细胞是具有颗粒的淋巴细胞，在病毒感染防御和肿瘤免疫监测中发挥重要作用。然而，癌症患者的 NK 细胞功能受损。聚肌胞苷酸[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，细胞内 poly(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 细胞细胞溶解的敏感性增加，同时 MICA/B 和 Fas 的表达上调。此外，与未经处理的肿瘤细胞上清液处理的 NK 细胞相比，poly(I:C)转染的肿瘤细胞上清液可显著增强 NK 细胞对肿瘤细胞的细胞溶解活性，以及 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。进一步的研究表明，poly(I:C)转染的胃腺癌细胞产生的 I 型干扰素 (IFN) 在这个过程中起着重要作用。我们的研究结果表明，细胞内 poly(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 poly(I:C)成为治疗胃腺癌的有前途的治疗药物。
