MICA脱落与肿瘤免疫逃逸肿瘤免疫治疗新靶标和新策略-药学进展.PDFVIP

PROGRESS IN PHARMACEUTICAL SCIENCES 2014,38 12 :905-909 ( ) 905 MICA 脱落与肿瘤免疫逃逸：肿瘤免疫治疗 新靶标和新策略 赵欣，ACHEAMPONG D. O.，张娟 * ，王旻 ** （中国药科大学天然药物活性物质与功能国家重点实验室 , 江苏 南京 210009） [ 摘要 ] MHC Ⅰ类链相关分子（MICA）是自然杀伤细胞和 T 细胞上 NKG2D 受体的主要活化性配体，在上皮源性肿瘤细胞表面过表达。 NKG2D 与 MICA 的结合可有效刺激效应细胞对肿瘤细胞的细胞毒作用。然而，临床观察表明，MICA 会在肿瘤的增殖过程中脱落而形成可 溶性 MICA（sMICA），这被认为是肿瘤细胞逃脱 NKG2D 介导的免疫监视的重要原因。综述在肿瘤细胞中 MICA 和 NKG2D 的表达与功能、 sMICA 的形成与肿瘤免疫逃逸的关联以及介导 MICA 脱落的机制，由此探讨肿瘤免疫治疗的新靶点和新策略。 [ 关键词 ] MHC Ⅰ类链相关分子；NKG2D 受体；MICA 脱落；肿瘤细胞；自然杀伤细胞；免疫逃逸；药物靶点 [ 中图分类号 ] R730.51 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2014）12-0905-05 MICA Shedding and Tumor Immune Escape: the Novel Target and Novel Strategy for Tumor Immunotherapy ZHAO Xin, ACHEAMPONG D. O., ZHANG Juan, WANG Min ( State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China) [Abstract] MHC class I chain-related molecule A(MICA) is one of the major activating ligands of NKG2D(natural killer group 2, member D) receptor on natural killer (NK) cells and T cells., which is overexpressed on the surface of tumor cells of epithelial origin. The cytotoxic effect of the effector cells on tumor cells could be mediated by the interaction of MICA with NKG2D. However, clinical researches have suggested that MICA will shed foming soluble MICA (sMICA) during the process of tumor proliferation, which is recognized as the major reason for tumor to escape NKG2D- mediated immunosurveillance. The expressions and functions of MICA and NKG2D, the association of the formation of sMICA with tumor immune escape and the mechanism of MICA shedding in tumor cells were reviewed, discussing the novel target and novel strategy for tumor immunotherapy . [K