中文摘要：

目的研究胆管癌中主要组织相容复合体Ⅰ类分子相关蛋白A/B（majer histocompatibility cemplex classⅠmolecule associated protein A/B,MICA/B）的表达改变对胆管癌细胞逃逸NK细胞杀伤的影响。方法收集89例胆管癌组织标本,采用免疫组织化学染色检测MICA/B的表达,分析其与临床病理特征、预后的相关性。体外胆管癌细胞与NK细胞（自然杀伤细胞）共培养,通过转染干预癌细胞中MICA/B的表达,观察NK细胞的杀伤作用。结果免疫组化提示MICA在61.8%（55/89）胆管癌组织中呈低表达,而57.3%（51/89）胆管癌中MICB呈低表达。MICA、MICB低表达分别与胆管癌的分化程度（P=0.019,P=0.024）、T分级（P=0.000,P=0.026）、淋巴结转移（P=0.028,P=0.017）,以及TNM分期（P=0.007,P=0.008）显著相关,提示MICA/B低表达与肿瘤侵袭转移特性显著相关。Kaplan-Meier分析提示MICA/B的表达水平与无瘤生存时间（P=0.002 6,P=0.005）、总生存时间（P=0.000 7,P=0.000 3）显著相关。体外胆管癌细胞与NK细胞共培养,癌细胞中MICA/B过表达显著增加NK细胞对癌细胞的杀伤作用,而干扰MICA/B的表达可以减弱NK细胞的杀伤作用。结论胆管癌中MICA/B低表达与侵袭转移病理特性显著相关,胆管癌细胞可通过下调MICA/B逃逸NK细胞的杀伤。

英文摘要：

Objective To investigate the expression levels of MICA/B in cholangiocarcinoma tissues and explore whether abnormal MICA/B expression helps the eholangiocarcinoma cells to evade immune surveillance by natural killer （NK） cells. Methods The expression levels of MICA and MICB were detected by immunohistoehemieal staining in 89 specimens of cholangioearcinoma, and their correlations with the clinieopathological features and prognosis of the patients were analyzed. Cholangiocarcinoma cells with RNA interference-mediated down-regulation of MICA/B or with lentivirus-mediated MICA/B over-expression were co-cultured with NK cells, and the changes in the cytotoxicity of NK cells were observed. Results Immunohistochemistry showed low MICA expression in 61.8% （55/89） of the cholangiocarcinoma tissues and low MICB expression in 57.3% （51/89） of the tissues. Low expression levels of MICA and MICB were closely correlated with the histological grade （ P = 0. 019 and 0. 024 ） , T classification （ P = 0. 000 and 0. 026）, lymph node metastasis （ P = 0. 028 and 0. 017 ）, and TNM staging （ P = 0. 007 and 0. 008 ） of the tumors. Kaplan-Meier analysis showed that the expression levels of MICA/B were significantly correlated with the overall survival time （ P = 0. 000 7 and 0. 000 3 ） and metastasis-free survival time （ P = 0. 002 6 and 0. 005 ） of the patients. In the co-cuhure system of cholangiocarcinoma and NK cells, over-expression of MICA/B significantly enhanced the killing effect of NK cells against cholangiocarcinoma cells, while down- regulation of MICAJB obviously attenuated the killing effect of NK cells. Conclusion Low expression levels of MICA/B are significantly associated with the invasion and metastatic capacities of cholangiocarcinoma and help the cholangiocarcinoma cells to evade immune surveillance by NK cells.