Lobaplatin alters antitumor immunity and upregulates PD⁃L1 expression in HCC
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    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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SHA Bowen, WANG Zeng, ZHOU Jinren, RAO Jianhua, CHENG Feng. Lobaplatin alters antitumor immunity and upregulates PD⁃L1 expression in HCC[J].,2021,(4):503-508.

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  • Received:October 26,2020
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  • Online: April 29,2021
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