Prognostic significance and functional implication of immune activating receptor NKG2D in gastric cancer
Prognostic significance and functional implication of immune activating receptor NKG2D in gastric cancer
复制标题
免疫激活受体NKG2D在胃癌中的预后意义及功能意义
DOI：
10.1016/j.bbrc.2017.04.104
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发表时间：
2017
影响因子：
3.1
通讯作者：
Li Jin
中科院分区：
文献类型：
--
作者：
Lin Fengjuan;Dai Congqi;Ge Xiaoxiao;Tang Wenbo;Lin Ying;Wang Yan;Li Jin
NKG2D是一种表达在CD8+T淋巴细胞上的激活受体，通过与其配体MICA/B和ULBPs结合，作为共刺激分子而触发抗肿瘤免疫激活。目前，NKG2D在胃癌中的生物学作用和临床意义尚不清楚。本研究旨在探讨NKG2D在胃癌组织中的表达及其与临床预后和生物学功能的关系。采用实时荧光定量聚合酶链式反应(Real-Time PCR)技术，对上海肿瘤中心2007-2010年间139例胃癌患者配对的癌组织及癌旁组织中NKG2D的表达进行分析。NKG2D的表达与任何临床特征参数无关。高NKG2D水平与较好的预后显著相关(OS组P=0.018，DFS组P=0.041)。单因素COX回归模型显示，NKG2D基因高表达可使胃癌患者的风险降低43%(HR=0.57，CI(0.36~0.91)，P=0.019)。多因素分析显示，高NKG2D水平与较长的OS显著相关(HR=0.59，CI(0.363~0.96)，P=0.034)，独立于其他预后因素，包括Lauren分类、神经浸润、血管/淋巴侵犯、TNM分期。与癌细胞共同孵育后，CD8+T细胞中NKG2D的表达明显下调。功能研究表明，封闭NKG2D或其配体ULBP-2均可抑制CD8+T细胞的肿瘤杀伤活性。结果表明，NKG2D受体可作为判断胃癌预后的独立指标。此外，NKG2D表达降低可能是胃癌肿瘤免疫逃逸的机制。
NKG2D, an activating receptor expressed on CD8+T lymphocytes, serves as a co-stimulation molecule by engagement with its ligands MICA/B and ULBPs to trigger immune activation against tumors. Currently, the biological function and clinical significance of NKG2D in gastric cancer remains unexplored. The study aims to investigate the expression of NKG2D in gastric cancer in association with clinical prognosis and its biological function. Real-time PCR was used to analyze NKG2D expression in paired cancer and adjacent non-malignant tissues in 139 gastric cancer patients between 2007 and 2010 in Shanghai Cancer Center. NKG2D expression showed no association with any clinical characteristic parameters. High NKG2D level was significantly associated with better outcome (P= 0.018 for OS,P= 0.041 for DFS). Using univariate Cox regression model, high NKG2D mRNA resulted in 43% risk reduction in gastric cancer patients (HR = 0.57, CI (0.36–0.91),P= 0.019). High NKG2D level displayed a significant association with longer OS in the multivariate analysis (HR = 0.59, CI (0.363–0.96),P= 0.034), independent of other prognostic factors including Lauren classification, neural infiltration, vascular/lymphatic invasion, TNM stage. Upon co-incubation with cancer cells, NKG2D expression in CD8+T cells was markedly down-regulated. Functional study suggested that either blocking NKG2D or its ligand ULBP-2 could suppress tumor-killing activity of CD8+T cells. Our data showed that NKG2D receptor could be an independent favorable prognostic indicator for gastric cancer. Furthermore, decreased NKG2D expression might be the mechanism underlying immune evasion by tumors in gastric cancer.