肝癌活化的星状细胞促进树突状细胞DIgR2表达致肝癌免疫抑制的研究

项目名称： 肝癌活化的星状细胞促进树突状细胞DIgR2表达致肝癌免疫抑制的研究

项目编号： No.81472331

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 夏云红

作者单位： 安徽医科大学

项目金额： 70万元

中文摘要： 肝细胞癌(HCC)的局部免疫抑制微环境在肝癌的复发转移中发挥了重要作用。近来研究提示肝星状细胞(HSC)在肝的免疫抑制中发挥着独特的作用，体外培养活化的HSC能抑制DC功能，致肝脏免疫耐受，DC表面的抑制性受体DIgR2是DC免疫调控机制的一条新途径。但HCC内HSC(tHSC)对DC的调控作用及其机制还不清楚。我们以前工作表明tHSC诱导T细胞凋亡是HCC免疫抑制的部分机制。本课题采用大鼠HCC模型，分离tHSC和骨髓DC(mDC)，应用流式细胞术、免疫组化、Western blot、[3H]TdR掺入、51Cr释放实验和siRNA干预等研究来证明tHSC通过促进mDC表面DIgR2的表达抑制mDC的功能，进而导致T细胞活化抑制，可能是HCC免疫抑制的部分机制。本研究以期发现HCC免疫抑制新机制以及靶向调控DIgR2表达来恢复tHSC对mDC的功能抑制，为肝细胞癌免疫治疗提供新的途径。

中文关键词： C09_肝和肝内胆管肿瘤；肝星状细胞；树突状细胞相关受体；T细胞；免疫抑制

英文摘要： Local immunosuppressive microenvironment in hepatocellular carcinoma (HCC) plays an important role in the recurrence and metastasis of HCC. Recent studies suggest that hepatic stellate cells (HSC) play a unique role in hepatic immune suppression. Activated HSC cultured in vitro can inhibit DC function and induce immune tolerance in liver. Inhibitory receptors DIgR2 on the surface of DC is a new way about DC immune regulation mechanism. However, regulatory role and mechanism of HSC in HCC (tHSC) on DC is not clear. Our previous work showed that the apoptosis of T cells induced by tHSC is the part mechanism of HCC immune suppression. We utilized the rat HCC model that tHSC and bone marrow DC (mDC) were separated. Flow cytometry, immunohistochemistry, Western blot, [3H]TdR incorporation, 51Cr assay and siRNA in vitro and in vivo intervention were applied to prove that tHSC inhibited mDC function through the expression promotion of DIgR2 on mDC surface, and resulted in the activation inhibition of T cells in HCC. Therefore, the above may be part of the immune suppression mechanism. This study can find the new mechanism of HCC immune suppression and restore tHSC on the inhibition of mDC function by targeting DIgR2 expression regulation.This research provided a new way for the immune treatment of HCC.

英文关键词： Liver and intrahepatic bile duct tumors;hepatic stellate cells;DIgR2;T cells;Immunosuppression