CpG-ODN通过调控细胞免疫显著增强热休克蛋白肿瘤疫苗诱导的抗肿瘤免疫效应  

CpG-ODN enhanced antitumor immune effect induced by hyperthermia generated tumor cell vaccine

作　　者：张莹莹[1] 王晓文[2] 唐劲天[2] ZHANG Ying-Ying;WANG Xiao-Wen;TANG Jin-Tian(Department of Oncology,Xiangya Hospital,Central South University,Changsha 410008,China;Institute of Medical Physics and Engineering,Department of Engineering Physics,Tsinghua University,Beijing 100084,China)

机构地区：[1]中南大学湘雅医院肿瘤科,湖南长沙410078 [2]清华大学工程物理系医学物理与工程研究所,北京100084

出　　处：《转化医学电子杂志》2018年第9期1-5,共5页E-Journal of Translational Medicine

基　　金：湖南省科技厅重点计划专项(2016JC2073)

摘　　要：目的:尝试将新型免疫佐剂Cp G-ODN与热休克蛋白肿瘤疫苗联合对小鼠进行免疫接种,以期利用Cp G-ODN的免疫增强效应提高热休克蛋白疫苗的疗效。方法:制备B16黑色素瘤的C57BL/6小鼠模型,实验组预先用热处理后富含热休克蛋白70(HSP70)的B16细胞瘤苗联合免疫佐剂Cp G-ODN注射到小鼠皮下行免疫接种,与对照组对比观察小鼠肿瘤的生长情况,检测小鼠外周血T淋巴细胞亚群的分布、脾淋巴细胞分泌Th1型细胞因子的活性以及CTL特异性细胞毒杀伤效率,以评价免疫应答反应的强弱。结果:接受联合免疫治疗的小鼠能产生较强的抗黑色素瘤免疫应答,35%的小鼠肿瘤未长出,已出瘤小鼠与对照组相比生存期明显延长,差异有统计学意义(P<0.05)。联合免疫组小鼠外周血CD4+/CD8+的值升高,脾淋巴细胞Th1型细胞因子分泌活性以及CTL特异性细胞毒杀伤效率均显著增强(P<0.01),但调节性T细胞亚群比例各组间无明显差异(P>0.05)。结论:免疫活性物质Cp G-ODN可显著增强热休克蛋白肿瘤疫苗在小鼠体内诱导的免疫应答,激发特异性抗肿瘤细胞毒作用,抑制黑色素瘤的生长。Objective： In this study, a novel immunoadjuvant CpG-ODN was combined with a heat shock protein tumor vaccine to immunize mice, in order to improve the efficacy of heat shock protein vaccine by using the immune enhancement effect of CpG ODN. Methods： The C57BL/6 mouse model attached by B16 cells was prepared. The experimental group was pre-treated with B16 cell vaccine supplemented with heat shock protein 70 （HSP70） and CpG ODN injection into the mouse skin. The growth of mouse tumors was observed; the distribution of T lymphocyte subsets in peripheral blood of mice, the activity of Thl type cytokines secreted by spleen lymphocytes, and the specific cytotoxicity of CTL were detected to evaluate immune response. Results： Mice receiving co-immunization can produce a strong anti-melanoma immune response. A total of 35% of the mice had no tumor growth. The survival time of the tumor-bearing mice was significantly longer than that of the control group, and the difference was statistically significant （P〈0.05）. The ratio of CD4＋/CD8＋ in peripheral blood of the mice in the combined immunization group was increased, and the Thl cytokine secretion activity and CTL-specific cytotoxicity of spleen lymphocytes were significantly increased （P〈0.01）. There was no significant difference of the proportion of regulatory T cell subsets between the groups （P〉0.05）. Conclusion： The immunologically active substance CpG-ODN can significantly enhance the immune response induced by the heat shock protein tumor vaccine in mice, stimulate specific anti-tumor cytotoxicity, and inhibit the growth of melanoma.

关 键 词：CPG-ODN 肿瘤细胞疫苗 热休克蛋白 抗肿瘤免疫应答 

分 类 号：R73-3[医药卫生—肿瘤]