膜型Tim-3分子促进荷瘤小鼠抗肿瘤免疫应答的研究  

Membran-type Tim3 Promotes Anti-turmor Immunity in Turmor-bearing Mice

作　　者：许朝旭[1] 张桂梅[1] 黄波[1] 冯作化[1] 

机构地区：[1]华中科技大学同济医学院基础医学院生物化学与分子生物学系,武汉市430030

出　　处：《医学分子生物学杂志》2007年第3期200-203,共4页Journal of Medical Molecular Biology

基　　金：国家自然科学基金(No.30471587)~~

摘　　要：目的研究膜型Tim-3分子对H22肝癌细胞生长的抑制效应,探讨膜型Tim-3分子对荷瘤小鼠免疫系统的影响。方法以H22肝癌细胞接种于BALB/c小鼠大腿肌肉建立小鼠实体瘤模型,采用原位注射裸DNA的方法在小鼠体内表达膜型Tim-3进行基因治疗,观察Tim-3对肿瘤生长的抑制作用;采用RT- PCR技术在肿瘤生长不同时期检测Tim-3对4-1BB、IFN-γ、galectin-9等免疫相关基因表达的影响;流式细胞术检测膜型Tim-3对脾细胞增殖活性及细胞毒活性的影响;观察Tim-3+4-1BBL协同抗肿瘤作用。结果体内转染表达Tim-3对肿瘤的生长有明显的抑制作用。流式细胞术结果显示,在小鼠荷瘤早期,Tim-3可提高脾细胞在特异性抗原刺激下的增殖反应和对H22肿瘤细胞的细胞毒作用;Tim-3与4-1BBL协同作用时抗肿瘤作用更加明显。结论膜型Tim-3可在免疫启动阶段作为正向免疫调节因子增强抗肿瘤免疫应答,并可与4-1BBL协同产生更强的抑瘤效应。Objective The aim of this study is to explore the inhibitory effect of transmembrane Tim-3 on H22 hepatocarcinoma and the potential effect on immune system of mice loaded with H22 hepatocarcinoma. Methods Tumor model was established by inoculation of H22 hepatocarcinoma cells at the hind thigh of BALB/c mice. Recombinant vector plasmids were transfected at the same site for gene therapy by injection. Inhibitory effect of Tim-3 on tumor growth was observed. A panel of genes including 4-1BB, IFN-γ/and galectin-9 from tumor tissues at different time points were analyzed by RT-PCR. The proliferation and cytotoxicity of splenocytes after Tim-3 transfection were evaluated by flow cytometry. Synergistic effect of Tim-3 with 4-1 BBL against tumor was also evaluated. Results Growth of tumor was suppressed evidently with the transfection of Tim-3. Flow cytometry showed that the proliferation of splenocytes and cytolysis to tumor cells detected in early phase of tumor development were enhanced in the presence of Tim-3, and this anti-tumor effect was further improved by the combined use of Tim-3 with 4-1 BBL. Conclusion Transmembrane Tim3 may act as a positive immunoregulator in the initiation of immunity to enhance anti-tumor immune responses and has synergistic effect with 4-1BBL in anti-tumor immunity.

关 键 词：Tim-3分子 4-1 BB GALECTIN-9 抗肿瘤免疫 

分 类 号：R392.33[医药卫生—免疫学]