胶质瘤细胞诱导肿瘤相关成纤维细胞表达程序性细胞凋亡蛋白-1配体  

Role and mechanism of glioma cells in expression of PD-L1 in fibroblasts cells

作　　者：李明国 刘丛[2] 吴谦 李兴华 杨福兵 游国亮 LI Mingguo;LIU Cong;WU Qian;LI Xinghua;YANG Fubing;YOU Guoliang(Department of Neurosurgery,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院神经外科,四川泸州646000 [2]内江市第一人民医院神经外科,四川内江646000

出　　处：《实用医学杂志》2019年第15期2384-2388,共5页The Journal of Practical Medicine

基　　金：四川省卫生厅项目(编号:17PJ188)

摘　　要：目的探讨肿瘤细胞对成纤维细胞程序性死亡受体1配体(programmed death-ligand 1,PD-L1表达水平的影响及相关机制。方法将脑原代成纤维细胞种在孔板中,将胶质瘤细胞接种于Transwell上室,或直接加入胶质瘤细胞来源外泌体或条件培养基。流式细胞术检测成纤维细胞PD-L1表达水平变化。结果胶质瘤与脑原代成纤维细胞共培养,可诱导成纤维细胞α-SMA表达上调,共培养2、4和6 d,成纤维细胞PD-L1阳性细胞比例逐渐增高,分别为(10.40±1.31)%、(48.67±2.19)%和(98.17±0.78)%,明显高于对照组(0.70±0.37)%,差异具有统计学意义。将外泌体与成纤维细胞共培养6 d,10、20和40μg/mL组成纤维细胞PD-L1阳性率分别为(18.40±11.45)%、(38.67±2.19)%和(68.17±7.78)%,明显高于对照组(2.37±0.98)%,差异具有统计学意义。而去除外泌体后的肿瘤细胞条件培养基诱导成纤维细胞表达PD-L1的能力大大降低,共培养2、4和6 d,成纤维细胞PD-L1阳性率分别为(12.53±1.22)%,(13.93±1.59)%和(13.87±3.02)%。结论胶质瘤细胞可诱导成纤维细胞向癌相关成纤维细胞转化,并可能通过外泌体介导成纤维细胞表达PD-L1。Objective To evaluate the role and mechanism of glioma cells in the expression of PD-L1 in fibroblasts cells. Methods The brain primary fibroblast cells were seeded in the culture plate,and glioblastoma cells or glioblastoma cells derived exosomes were added into the upper chamber of transwell champer. And the expression of PD-L1 in fibroblasts were detected by flow cytometry. Results The expression of α-SMA in fibroblast cells were up-regulated by glioblastoma cells in the co-culture system. Moreover,the percentage of PD-L1+ fibroblast cells was(10.40 ± 1.31)%,(48.67 ± 2.19)% and(98.17 ± 0.78)% after co-cultured with glioblastoma cells for 2,4 and 6 days respectively,which were significantly higher than that of control group(0.70 ± 0.37)%. The percentage of PD-L1+ fibroblast cells was(18.40 ± 11.45)%,(38.67 ± 2.19)% and(68.17 ± 7.78)% after treated with 10,20 and 40 μg/mL respectively for 6 days,which were significantly higher than that of control group(2.37± 0.98)%. After treated with exosomes-free glioblastoma cells conditional culture medium for 2,4 and 6 days,the percentage of PD-L1+ fibroblast cells were(12.53 ± 1.22)%,(13.93 ± 1.59)% and(13.87 ± 3.02)% respectively.Conclusion The expression of PD-L1 in cancer-related fibrosis,which is induced by glioblastoma cells,is upregulated by glioblastoma cells through their secreted exosomes.

关 键 词：胶质瘤 成纤维细胞 癌相关成纤维细胞 外泌体 程序性细胞凋亡蛋白-1配体 肿瘤免疫 

分 类 号：R739.4[医药卫生—肿瘤]