洛铂对肝癌肿瘤免疫及PD⁃L1表达的影响
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国家自然科学基金(82070675,81871259)


Lobaplatin alters antitumor immunity and upregulates PD⁃L1 expression in HCC
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    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。

    Abstract:

    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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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(自然科学版),2021,(4):503-508

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  • 收稿日期:2020-10-26
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  • 在线发布日期: 2021-04-29
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