Clinical significance of the immunostimulatory MHC class I chain-related molecule A and NKG2D receptor on NK cells in pancreatic cancer
Clinical significance of the immunostimulatory MHC class I chain-related molecule A and NKG2D receptor on NK cells in pancreatic cancer
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DOI：
10.1007/s12032-010-9480-9
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发表时间：
2011-06-01
期刊：
影响因子：
3.4
通讯作者：
Sun, Weijia
中科院分区：
文献类型：
--
作者：
Duan, Xiaohui;Deng, Langmei;Sun, Weijia
本研究旨在探讨胰腺癌组织中NK细胞表面MHC I类链相关分子A（云母）和NKG 2D受体表达的临床意义。我们使用免疫组织化学方法比较了云母在恶性（n = 103）、炎症（n = 28）和正常（n = 17）胰腺组织中的表达，并评估了胰腺癌患者（n = 103）、慢性胰腺炎患者（n = 28）和健康志愿者（n = 43）的可溶性云母（sMICA）和NK细胞上NKG 2D表达的血清水平。云母在胰腺癌组织中的表达率为89.3%，而在炎症组织和正常胰腺组织中的表达率较低。sMICA水平在晚期胰腺癌患者中经常升高。sMICA升高与NKG 2D表达下调和NK细胞活性受损相关。成功的肿瘤切除显著降低了血清sMICA水平，增加了NKG 2D表达; sMICA水平变化与NKG 2D表达变化之间呈负相关。云母表达、术前sMICA水平和NKG 2D强度被认为是切除胰腺癌的独立预后因素。本研究支持云母释放对胰腺癌恶性进展的临床意义。胰腺癌的成功肿瘤切除可能对NKG 2D介导的抗肿瘤免疫产生有益影响。我们的研究结果还表明，NK细胞上的sMICA和NKG 2D表达可能有助于在诊断时间点识别风险患者。
The aim of this paper was to determine the clinical significance of the MHC class I chain-related molecule A(MICA) and NKG2D receptor on NK cells in pancreatic cancer. We compared MICA expression in malignant (n = 103), inflammatory (n = 28), and normal (n = 17) pancreatic tissues using immunohistochemistry and assessed serum levels of soluble MICA (sMICA) and NKG2D expression on NK cells in patients with pancreatic cancer (n = 103), in patients with chronic pancreatitis (n = 28), and in healthy volunteers (n = 43). Expression of MICA was detected in 89.3% of pancreatic cancer tissues, whereas fewer were expressed in inflammatory and normal pancreatic tissues. The levels of sMICA were frequently elevated in patients with advanced pancreatic cancer. The elevation of sMICA was associated with down-regulated NKG2D expression and impaired activity of NK cells. The successful tumor resection significantly decreased serum levels of sMICA and increased the NKG2D expression; there was an inverse correlation between change in sMICA levels and that in NKG2D expression. MICA expression, preoperative sMICA levels and NKG2D intensity were found to be independent prognostic factors in resected pancreatic cancer. This study supports the clinical significance of release of MICA for the malignant progression of pancreatic cancer. The successful tumor resection for pancreatic cancer may have a beneficial effect on NKG2D-mediated antitumor immunity. Our results also suggest sMICA and NKG2D expression on NK cells may be useful to identify risk patients at time point of diagnosis.