CpG-ODN加强树突状细胞疫苗治疗小鼠膀胱肿瘤的实验研究

Study on enhancement of DC vaccine to murine bladder carcinoma by CpG oligodeoxynucleotide

目的探讨含CpG序列的寡脱氧核糖核苷酸(CpG-ODN)对树突状细胞(DC)疫苗治疗小鼠膀胱肿瘤作用的影响。方法应用CpG-ODN作为DC成熟的刺激信号,体外诱导DC成熟,BTT739膀胱肿瘤细胞抗原提取物致敏DC制备DC疫苗,建立BTT739荷瘤小鼠动物模型,随机分为磷盐酸缓冲液(PBS)对照组、DC疫苗组、CpG-ODN组、DC+CpG-ODN联合治疗组,于肿瘤细胞接种后第7、14天给予治疗,每组分2个亚组,分别用于测量瘤重、体积及用于观察荷瘤小鼠存活情况。流式细胞仪检测肿瘤组织中浸润性树突状细胞(TIDC)表面共刺激分子CD80、CD86的表达。结果第2次治疗7 d后,联合治疗组平均瘤重及平均肿瘤体积均显著低于其余3个组(P<0.01),荷瘤小鼠生存期显著长于其余3个组(P<0.05)。肿瘤组织中TIDC表面CD80、CD86表达水平,联合治疗组略高于CpG-ODN组,差异无统计学意义(P>0.05),但均显著高于PBS对照组和DC疫苗组(P<0.05)。结论CpG-ODN可增强负载肿瘤抗原的DC疫苗对膀胱肿瘤荷瘤小鼠的抑瘤效应和生存期延长作用,其机制主要是通过诱导DC成熟。

Objective To investigate whether CpG oligodeoxynucleotide （CpG-ODN） can affect the immunotherapeutic effects of DC vaccine on murine bladder carcinoma. Methods CpG-ODN was used to promote maturation of DCs in vitro. DCs were plused with BTT739 cell antigen and I）C vaccine was prepared. After the BTT739 bladder tumor model in 48 T739 mice were successfully established, phosphate buffered saline,DC vaccine, CpG-ODN and DC--CpG-ODN were injected respectively into the margins of the tumor（peritumoral） on 7 d and 14 d after tumor cells inoculation. Tumor weight,volume and the life span of mice were recorded. The expression levels of CD80 and CD86 on TIDC of tumor tissues were detected by flow cytometry. Results On 7 d after the sec- ond injection,average tumor weight and average tumor volume in DC＋CpG-ODN group was lower than those in control group,DC group and CpG-ODN group（P^0.01）. The life span of mice in DC＋CpG-ODN group was significantly longer than that in the oth er three groups（P^0.05）. The expression levels of CD80 and CD86 on TIDC in DC^CpG-（）DN group and CpG OI）N group were higher than that in control group and DC group（P^O. 05）. Conclusion CpG-ODN can enhance the immunolherapeutic effects of DC vaccine on inhibiting tumor growth and prolonging the living time of T739 mice with BTT739 bladder lumor via inducing the maturation of DC.