X-盒结合蛋白1和热休克蛋白靶向的树突状细胞疫苗对肾癌肿瘤免疫治疗作用的比较研究  

Comparative study of immunotherapy with heat shock protein and X-box binding protein 1targeting dendritic cell vaccine against renal cancer

作　　者：潘炜[1] 蔡鹤龄[1] 吴运 PAN Wei;CAI Heling;WU Yun(Department of Urology,People＇s Hospital of Huangpi District Wuhan, Wuhan, 430300, Chin)

机构地区：[1]武汉市黄陂区人民医院泌尿外科,武汉430300

出　　处：《临床泌尿外科杂志》2018年第6期472-476,共5页Journal of Clinical Urology

基　　金：武汉市临床医学科研项目(编号WX14C25)

摘　　要：目的:应用树突状细胞(DC)与X-盒结合蛋白1(XBP1)共培养制备XBP1-DC疫苗,通过与热休克蛋白70(HSP70)-DC疫苗对GRC2细胞的免疫杀伤作用进行比较,初步探讨应用XBP1蛋白与DC共培养制备融合瘤疫苗的可行性。方法:从肾癌患者的外周血中分离出外周血单核细胞(PBMC),经体外培养诱导为DC。以HSP70和XBP1与DC共培养制备HSP70-DC和XBP1-DC融合瘤疫苗。用HSP70-DC和XBP1-DC疫苗分别刺激患者外周血分离的T淋巴细胞,采用ELISA法检测所产生的CTL反应。以经HSP70-DC和XBP1-DC刺激形成的CTL作为效应细胞,以正常细胞、GRC2为靶细胞,测不同效靶比(10:1、20:1)下,效应细胞杀伤靶细胞的能力。结果:PBMC经细胞因子诱导后,CD1a、CD86、CD83、HLA-DR表达水平均显著高于诱导前表达水平(P<0.05)。与DC组比较,XBP1-DC疫苗致敏后,CTL细胞均释放INF-γ显著增加,差异有统计学意义(P<0.05),而与HSP70-DC疫苗致敏的CTL细胞比较,XBP1-DC释放的INF-γ差异无统计学意义(P>0.05)。随着效靶比的升高,各组CTL细胞对GRC2细胞和RCC细胞的杀伤率均相应提高,差异均有统计学意义(P<0.05)。在不同效靶比时,HSP-DC和XBP1-DC免疫的CTL对GRC2和GCC的杀伤作用差异均无统计学意义(P>0.05)。结论:XBP1与DC共培养后,能增强DC的抗原呈递能力,增强T淋巴细胞分泌细胞因子的能力,从而特异性杀伤肾癌GRC2细胞系,且杀伤作用与HSP70-DC融合瘤疫苗一致,在抗肿瘤杀伤作用中具有一定的可行性。Objective：To prepare XBP1-DC vaccine using DC and XBP1 protein were co-cultured,compared with HSP70-DC vaccine on GRC2 cells,the application of XBP1 protein DC were co-cultured with the feasibility of preparing fusion vaccine.Method：Peripheral blood mononuclear cells were isolated from peripheral blood of patients with renal cell carcinoma and induced by DC in vitro.HSP70-DC and XBP1-DC fusion tumor vaccines were prepared by co-culture of HSP70 and XBP1 with DC.T lymphocytes isolated from peripheral blood of patients were stimulated by HSP70-DC and XBP1-DC vaccine,and the CTL reaction was detected by ELISA.CTL,which was stimulated by HSP70-DC and XBP1-DC,was used as effector cell,and normal cells and GRC2 as target cells were used to measure the ability of effector cells to kill target cells under different target ratios（10∶1 and 20∶1）.Result：The expression levels of CD1 a,CD86,CD83 and HLA-DR in peripheral blood monocytes after induction of cytokines were significantly higher than those before induction,and the differences were statistically significant（P〈0.05）.Compared with the DC group,the CTL cells released INF-γafter the sensitization of XBP1-DC vaccine,and the difference was statistically significant（P〈0.05）.Compared with the HSP70-DC vaccine sensitized CTL cells,the INF-γreleased by XBP1-DC group was no significant（P〉0.05）.With the increase of target ratio,the killing rate of CTL cells and RCC cells in each group of GRC2 cells increased correspondingly,and the differences were statistically significant（P〈0.05）.There was no statistically significant difference in the killing effects of CTL and GCC on GRC2 and between HSP-DC and XBP1-DC at different target ratios（P〉0.05）.Conclusion：XBP1 co-cultured with DC,DC can enhance the antigen presenting ability,enhance the ability of T cell cytokine secretion,and specific cytotoxicity against renal cell carcinoma cell line GRC2,and cytotoxicity and HSP70-DC fusion vaccine,anti-tumor cytotoxic effect has certain feasibili

关 键 词：树突状细胞 X-盒结合蛋白1 热休克蛋白70 融合瘤疫苗 肾癌 

分 类 号：R737.11[医药卫生—肿瘤]