南京医科大学学报（自然科学版）2018，Vol.38Issue(1)：40-43,79,5.DOI:10.7655/NYDXBNS20180109
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 effect against pancreatic cancer
摘要
Abstract
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-L 1 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-γproduction was detected by ELISA.Pancreatic cancer tumor-bearing huSCID 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-L 1 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.关键词
胰腺癌/PD-L1/树突状细胞/疫苗Key words
pancreatic cancer/RNAi/PD-L1/DC vaccine分类
医药卫生引用本文复制引用
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（自然科学版）,2018,38(1):40-43,79,5.基金项目
国家自然科学基金(81302146) （81302146）
中国博士后基金(2016M591913) （2016M591913）
江苏省青年医学人才(QNRC2016732) （QNRC2016732）
江苏省自然科学基金(BK20161225) （BK20161225）
江苏省卫生计生委科研课题(H201620) （H201620）
苏州市科技计划(SYS201539) （SYS201539）
