文章摘要
沙博文,王 曾,周锦仁,饶建华,成 峰.洛铂对肝癌肿瘤免疫及PD⁃L1表达的影响[J].南京医科大学学报,2021,(4):503~508
洛铂对肝癌肿瘤免疫及PD⁃L1表达的影响
Lobaplatin alters antitumor immunity and upregulates PD⁃L1 expression in HCC
投稿时间:2020-10-26  
DOI:10.7655/NYDXBNS20210405
中文关键词: 肝癌  洛铂  PD⁃L1  抗肿瘤免疫
英文关键词: hepatocellular carcinoma  lobaplatin  PD⁃L1  antitumor immunity
基金项目:国家自然科学基金(82070675,81871259)
作者单位
沙博文 南京医科大学第一附属医院肝胆中心中国医学科学院肝移植重点实验室江苏 南京 210029 
王 曾 南京医科大学第一附属医院肝胆中心中国医学科学院肝移植重点实验室江苏 南京 210029 
周锦仁 南京医科大学第一附属医院肝胆中心中国医学科学院肝移植重点实验室江苏 南京 210029 
饶建华 南京医科大学第一附属医院肝胆中心中国医学科学院肝移植重点实验室江苏 南京 210029 
成 峰 南京医科大学第一附属医院肝胆中心中国医学科学院肝移植重点实验室江苏 南京 210029 
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中文摘要:
      目的:探讨洛铂(lobaplatin,LBP)对肝癌肿瘤免疫及程序性死亡配体1(prag rammed cell death 1 ligand,PD?L1)调控表达的作用及机制。方法:①73例肝细胞癌患者随机分为对照组(n=33)和洛铂组(n=40),两组均接受肝癌切除术,洛铂组术中腹腔灌注洛铂(50 mg),比较两组患者手术前后外周血淋巴细胞亚群变化。②Hep3B肝癌细胞以洛铂(16 μmol/L)处理24 h,流式细胞术测定人白细胞抗原Ⅰ类分子(human leucocyte antigenI,HLA?Ⅰ),抗原转运蛋白TAP?1、TAP?2表达。③Hep3B、SMCC?7721、HepG2肝癌细胞以洛铂(0、8、16 μmol/L)处理24 h,用Western blot、RT?qPCR测定其PD?L1、AKT、p?AKT表达情况。④将Hep3B肝癌细胞分为洛铂组(16 μmol/L)、AKT抑制剂组(洛铂16 μmol/L + MK2206 1 μmol/L)和对照组,处理24 h后Western blot测定PD?L1表达。结果:①洛铂组患者手术前后外周血CD4+、CD4+/CD8+比值升高,Treg细胞下降(P < 0.05)。对照组差异无统计学意义(P > 0.05)。②洛铂处理后,Hep3B肝癌细胞HLA?Ⅰ、TAP?1和TAP?2表达增高。③洛铂处理后,Hep3B、SMCC?7721、HepG2肝癌细胞PD?L1、p?AKT表达增加。④AKT抑制剂组Hep3B肝癌细胞PD?L1表达相比洛铂组下降。结论:洛铂可以提高肝癌患者抗肿瘤免疫,可能是通过上调肝癌细胞抗原呈递组件表达,增强肿瘤免疫原性导致。同时洛铂能够上调肝癌细胞PD?L1表达,其机制可能涉及AKT信号通路。
英文摘要:
      Objective:To explore the effects and mechanisms of lobaplatin on antitumor immunity and programmed cell death 1(PD?1)expression in hepatocellular carcinoma(HCC). Methods:①A total of 73 HCC patients were randomly divided into two groups:the lobaplatin group(50 mg lobaplatin in 100 ml sterile water was infused into abdominal cavity during liver cancer resection,n=40),and the control group(n=33). The changes in peripheral blood lymphocyte subsets were analyzed before and after surgery. ②The effects of lobaplatin(16 μmol/L)on the expression of HLA?I,TAP?1,TAP?2 in Hep3B cells were analyzed by flow cytometry. ③Hep3B,HepG2,SMMC?7721 cells treated with lobaplatin(0,8,16 μmol/L)for 24 h,then the expressions of PD?L1,AKT,p?AKT protein were analyzed by Western blot and RT?qPCR. ④the expression of PD?L1 in Hep3B cells treated with lobaplatin,or lobaplatin and AKT?inhibitor MK2206 or PBS was analyzed by Western blot. Result:①After intraperitoneal infusion of lobaplatin,the rates of CD4+ and CD4+/CD8+ increased(P < 0.05),Treg decreased(P < 0.05)in the peripheral blood. ②Lobaplatin upregulated the expression of HLA?I,TAP1,and TAP2 in Hep3B cells. ③Lobaplatin upregulated the expression of PD?L1,p?AKT protein in HepG2,SMCC?7721,and Hep3B cells. ④AKT?inhibitor MK2206 reduced the effect of lobaplatin on the up?regulation of PD?L1 expression in Hep3B cells. Conclusion:Lobaplatin can enhance the anti?tumor immunity of HCC patients,induce antigen presentation of liver cancer cells and increase the expression of PD?L1 through AKT signal pathway,so that lobaplatin maybe combine with immune checkpoint inhibitor to treat HCC.
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