1-甲基色氨酸联合树突状细胞疫苗对胰腺癌荷瘤小鼠的免疫作用  

Immunotherapeutic effects of 1-methyltroptophan combined with dendritic cells vaccine in mice with pancreatic carcinoma

作　　者：陈树波[1] 李元栋[1] 孔祥顺[1] 姬东辉[1] 宋兰英[1] 孙小芳[1] 

机构地区：[1]河北省邢台市人民医院肿瘤外一科,054031

出　　处：《中华实验外科杂志》2013年第9期1900-1902,共3页Chinese Journal of Experimental Surgery

基　　金：河北省邢台市科学技术研究与发展计划基金资助项目（2012ZZ031-1）

摘　　要：目的 观察l-甲基色氨酸（1-MT）联合树突状细胞（DC）疫苗对胰腺癌荷瘤小鼠的免疫作用.方法 建立小鼠胰腺癌模型,利用肿瘤细胞裂解物冲击DC制备DC疫苗,并根据是否与1-MT联合应用分组（n=8）,Western blot法检测荷瘤鼠肿瘤组织周围引流淋巴结（TDLNs）中Ⅰ吲哚胺2,3-双加氧酶（IDO）蛋白表达水平相对于正常对照组的变化.实时荧光定量聚合酶链反应（FQ-PCR）测量叉头样螺旋转录因子（Foxp3）在TDLNs及脾脏mRNA水平.结果 接受DC疫苗治疗的胰腺癌荷瘤鼠TDLNs中IDO表达为1.251±0.334,显著高于磷酸盐缓冲液（PBS）组（0.832±0.194）,同时TDLNs中Foxp3 mRNA表达水平显著提高（19.99 ±5.351,P＜0.05）.1-MT＋ DC疫苗联合应用组与DC疫苗组比较IDO表达受到抑制,Foxp3 mRNA表达水平显著降低（12.330±2.841）.结论 通过抑制IDO活性,1-MT可以有效抑制胰腺癌荷瘤鼠癌组织周围引流淋巴结及脾脏CD4＋ CD25＋调节性T细胞的数量增加,从而增强DC疫苗抗肿瘤作用.Objective To investigate the immunotherapeutic effects of 1-methyltroptophan （1-MT） combined with dendritic cells （DCs） vaccine in mice with pancreatic carcinoma.Methods Tumor models were established in C57BL/6 mice by subcutaneous injection of Pan02 cells.To prepare the DCs vaccine,DCs were pulsed with tumor cell lysate.This DCs vaccine,as a single agent or in combination with 1-MT,was administered to pancreas adenocarcinoma mice.The expression of indoleamine 2,3-dioxygenase （IDO） in tumor draining lymph nodes （TDLNs） and spleen in a murine pancreas adenocarcinoma model was detected by using Western blotting.The prevalence of regulatory T cells （Treg） in TDLNs and spleen in a murine pancreas adenocarcinoma model was investigated by using real-time fluorescent quantitative polymerase chain reaction （FQ-PCR）.Results After application of DCs vaccine,the expression of IDO （1.251 ±0.334） was considerably higer in TDLNs than in PBS group （P ＜0.05）.In 1-MT ＋DCs vaccine group,the expression of IDO （0.966 ± 0.248） was considerably lower in TDLN than in DCs vaccine group （P ＜ 0.05）.Conclusion 1-MT could effectively enhance anti-tumor efficacy of DCs pulsed with tumor cell lysate by down-regulating CD4 ＋ CD25 ＋ Tregs.

关 键 词：吲哚胺2 3-双加氧酶 胰腺癌 树突状细胞 疫苗 

分 类 号：R735.9[医药卫生—肿瘤]