胆管癌MICA/B的异常表达对NK细胞杀伤作用的影响

邓翔; 田峰; 赵鑫; 王曙光

doi:10.16016/j.1000-5404.201612054

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胆管癌MICA/B的异常表达对NK细胞杀伤作用的影响

更新时间：2026-02-09

- 胆管癌MICA/B的异常表达对NK细胞杀伤作用的影响
- Effect of abnormal expression of MICA /B in cholangiocarcinoma cells on cytotoxicity of natural killer cells
- 第三军医大学学报 2017年39卷第10期页码：977-982
- 作者机构：
  
  400038 重庆，第三军医大学西南医院全军肝胆外科研究所
- 作者简介：
  
  [王曙光, E-mail:shuguangwangxnyy@sina.com Wang Shuguang, E-mail: shuguangwangxnyy@sina.com
- 基金信息：
  
  国家自然科学基金面上项目(81472295)
- DOI：10.16016/j.1000-5404.201612054
  中图分类号： R392.3;R730.23;R735.8
- 收稿：2016-12-08，
  
  修回：2017-01-11，
  
  纸质出版：2017-05-30
- 稿件说明：
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邓翔, 田峰, 赵鑫, 等. 胆管癌MICA/B的异常表达对NK细胞杀伤作用的影响[J]. 第三军医大学学报, 2017,39(10):977-982.

Xiang Deng, Feng Tian, Xin Zhao, et al. Effect of abnormal expression of MICA /B in cholangiocarcinoma cells on cytotoxicity of natural killer cells[J]. Journal of Third Military Medical University, 2017, 39(10): 977-982.
邓翔, 田峰, 赵鑫, 等. 胆管癌MICA/B的异常表达对NK细胞杀伤作用的影响[J]. 第三军医大学学报, 2017,39(10):977-982. DOI： 10.16016/j.1000-5404.201612054.

Xiang Deng, Feng Tian, Xin Zhao, et al. Effect of abnormal expression of MICA /B in cholangiocarcinoma cells on cytotoxicity of natural killer cells[J]. Journal of Third Military Medical University, 2017, 39(10): 977-982. DOI： 10.16016/j.1000-5404.201612054.

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 class Ⅰ molecule 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（

＝ 0.019，

＝ 0.024）、T分级（

＝ 0.000，

＝ 0.026）、淋巴结转移（

＝ 0.028，

＝ 0.017），以及TNM分期（

＝ 0.007，

＝ 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（

＝ 0.002 6，

＝ 0.005）、总生存时间（

＝ 0.000 7，

＝ 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。

Abstract

Objective

To investigate the expression levels of MICA /B in cholangiocarcinoma tissues and explore whether abnormal MICA /B expression helps the cholangiocarcinoma cells to evade immune surveillance by natural killer (NK) cells.

Methods

The expression levels of MICA and MICB were detected by immunohistochemical staining in 89 specimens of cholangiocarcinoma

and their correlations with the clinicopathological 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 (

＝ 0.019 and 0. 024)

T classification (

＝ 0.000 and 0. 026)

lymph node metastasis (

＝ 0.028 and 0. 017)

and TNM staging (

＝ 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 (

＝ 0.000 7 and 0. 000 3) and metastasis-free survival time (

＝ 0.002 6 and 0.005) of the patients. In the co-culture 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 MICA/B 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.

关键词

Keywords

references

Mittal D, Gubin M M, Schreiber R D, et al. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape[J]. Curr Opin Immunol, 2014, 27: 16-25. DOI: 10.1016/j.coi.2014.01.004.

Schreiber R D, Old L J, Smyth M J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion[J]. Science, 2011, 331(6024): 1565-1570. DOI: 10.1126/science.1203486.

Duan S G, Cheng L, Li D J, et al. The role of MAPK-ERK pathway in 67-kDa laminin receptor-induced FasL expression in human cholangiocarcinoma cells[J]. Dig Dis Sci, 2010, 55(10): 2844-2852. DOI: 10.1007/s10620-009-1121-9.

Long E O, Kim H S, Liu D, et al. Controlling natural killer cell responses: integration of signals for activation and inhibition[J]. Annu Rev Immunol, 2013, 31: 227-258. DOI: 10.1146/annurev-immunol-020711-075005.

Raulet D H, Gasser S, Gowen B G, et al. Regulation of ligands for the NKG2D activating receptor[J]. Annu Rev Immunol, 2013, 31: 413-441. DOI: 10.1146/annurev-immunol-032712-095951.

Dambrauskas Z, Svensson H, Joshi M, et al. Expression of major histocompatibility complex class I-related chain A/B (MICA/B) in pancreatic carcinoma[J]. Int J Oncol, 2014, 44(1): 99-104. DOI: 10.3892/ijo.2013.2156.

Pende D, Cantoni C, Rivera P, et al. Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin[J]. Eur J Immunol, 2001, 31(4): 1076-1086. DOI: 10.1002/1521-4141(200104)31.

Camp R L, Dolled-Filhart M, Rimm D L. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization[J]. Clin Cancer Res, 2004, 10(21): 7252-7259. DOI: 10.1158/1078-0432.CCR-04-0713.

李大江, 陈健, 熊燕, 等.体外共培养体系中胆管癌细胞对内皮细胞的作用[J].中华消化外科杂志, 2009, 8(2): 127-129. DOI: 10.3760/cma.j.issn.1673-9752.2009.02.018.

Li D J, Chen J, Xiong Y, et al. Influence of cholangiocarcinoma cells on endothelial cells in a co-culture system[J]. Chinese Journal of Digestive Surgery, 2009, 8(2): 127-129. DOI:10.3760/cma.j.issn.1673-9752.2009.02.018.

Gui A, Kobayashi A, Motoyama H, et al. Impaired degradation followed by enhanced recycling of epidermal growth factor receptor causedby hypo-phosphorylation of tyrosine 1045 in RBE cells[J]. BMC Cancer, 2012, 12: 179. DOI: 10.1186/1471-2407-12-179.

Wang B, Wang Q, Wang Z, et al. Metastatic consequences of immune escape from NK cell cytotoxicity by human breast cancer stem cells[J]. Cancer Res, 2014, 74(20): 5746-5757. DOI: 10.1158/0008-5472.CAN-13-2563.

Peruzzi G, Masilamani M, Borrego F, et al. Endocytosis as a mechanism of regulating natural killer cell function: unique endocytic and trafficking pathway for CD94/NKG2A[J]. Immunol Res, 2009, 43(1-3): 210-222. DOI: 10.1007/s12026-008-8072-7.

Gavlovsky P J, Tonnerre P, Gerard N, et al. Alternative Splice Transcripts for MHC Class I-like MICA Encode Novel NKG2D Ligands with Agonist or Antagonist Functions[J]. J Immunol, 2016, 197(3): 736-746. DOI: 10.4049/jimmunol.1501416.

Pages F, Kroemer G. Prognostic impact of anticancer immune responses: an introduction[J]. Semin Immunopathol, 2011, 33(4): 317-319. DOI: 10.1007/s00281-011-0278-4.

Groh V, Rhinehart R, Randolph-Habecker J, et al. Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells[J]. Nat Immunol, 2001, 2(3): 255-260. DOI: 10.1038/85321.

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