文章摘要
蒋浩海,赵 鑫,赵 华,朱新国,李德春.靶向PD⁃L1分子的 RNAi增强树突状细胞疫苗对胰腺癌治疗作 用的实验研究[J].南京医科大学学报,2018,(1):40~43,79
靶向PD⁃L1分子的 RNAi增强树突状细胞疫苗对胰腺癌治疗作 用的实验研究
RNAi targeting PD⁃L1 enhances DC vaccination antitumor immunologic therateupic effectagainst pancreatic cancer
投稿时间:2016-10-31  
DOI:10.7655/NYDXBNS20180109
中文关键词: 胰腺癌  PD⁃L1  树突状细胞  疫苗
英文关键词: pancreatic cancer  RNAi  PD⁃L1  DC vaccine
基金项目:国家自然科学基金(81302146);中国博士后基金(2016M591913);江苏省青年医学人才(QNRC2016732);江苏省 自然科学基金(BK20161225);江苏省卫生计生委科研课题(H201620);苏州市科技计划(SYS201539)
作者单位
蒋浩海 苏州大学附属第一医院普外科江苏 苏州 215006 
赵 鑫 苏州大学附属第一医院普外科胰腺疾病研究中心江苏 苏州 215006 
赵 华 苏州大学附属第一医院普外科江苏 苏州 215006 
朱新国 苏州大学附属第一医院普外科江苏 苏州 215006 
李德春 苏州大学附属第一医院普外科胰腺疾病研究中心江苏 苏州 215006 
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中文摘要:
      目的:研究通过 RNA干扰敲减程序性死亡受体配体 1(programmed death receptor ligand 1,PD?L1)分子能否增强树 突状细胞疫苗对胰腺癌的治疗作用。方法:免疫组化法检测42例胰腺癌及对应胰腺组织中PD?L1的表达差异;纯化CD8+T细 胞和制备成熟的树突状细胞(DC),将低表达PD?L1的Panc?1细胞Panc?1/PD?L1?RNAi、阴性对照Panc?1/LV?Control细胞以及野 生型Panc?1细胞分别与CD8+T细胞+DC疫苗共同培养,检测细胞上清中干扰素(IFN)?γ表达水平;3组肿瘤细胞分别建立人源 化严重免疫缺陷(severe combined immunodeficiency,SCID)小鼠胰腺癌皮下移植瘤模型,以 DC疫苗为治疗手段进行尾静脉注 射,观察肿瘤生长情况。结果:免疫组化实验显示,胰腺癌组织较胰腺组织中PD?L1高表达,差异有统计学意义(P<0.001)。T 细胞反应实验显示,PD?L1敲减肿瘤细胞组与DC和CD8+T细胞共同培养的上清中IFN?γ表达水平明显高于其他2个对照组,差 异有统计学意义(P<0.001)。人源化SCID小鼠体内荷瘤实验显示,敲减PD?L1表达与应用DC疫苗治疗胰腺癌皮下移植瘤具 有协同作用。结论:胰腺癌较胰腺组织中PD?L1高表达,敲减胰腺癌细胞PD?L1表达与应用DC疫苗治疗可能是胰腺癌免疫治 疗的有效策略。
英文摘要:
      Objective:To investigate whether knocking down PD ? L1 expression can enhance the effects of DC vaccine to treat pancreatic cancer. Methods:PD?L1 expression in normal pancreatic tissues and pancreatic cancer tissue specimens were detected by immunohistochemistry in tumor specimen of 42 pancreatic carcinoma patients respectively. A Panc?1 cell line with low PD?L1 expression established by lentivirus mediated RNA interference targeting PD?L1 was named Panc? 1/PD?L1? RNAi. At the same time,negative control cells Panc?1/LV?Control and wide type Panc?1 cell line was used in this study. These three groups of pancreatic cancer cells were co?cultured with CD8+ T cells and mature DC,and then IFN?γ production was detected by ELISA. Pancreatic cancer tumor?bearing hu? SCID mice model was established. DC vaccination was performed to investigate tumor inhibition effects. Results:Higher expressions of PD ? L1 were detected in pancreatic carcinoma than in normal pancreatic tissue(P<0.001)detected by immunohistochemistry examination. In the T cell reaction study,IFN?γ production is much higher in the PD?L1 knocking down group than that in the other two control groups(P<0.001). In vivo,PD?L1 knocking down combined with DC vaccination could significantly prevent tumor growth in the hu?SCID model. Conclusion:PD?L1 is expressed higher in pancreatic cancer than in normal pancreatic tissue. Suppressing PD?L1 expression in cancer cells during DC vaccination might be a more efficient strategy in immunotherapy for pancreatic cancer
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