Killing efficiency affected by mutually modulated PD-1 and PD-L1 expression via NKT-hepatoma cell interactions.
Killing efficiency affected by mutually modulated PD-1 and PD-L1 expression via NKT-hepatoma cell interactions.
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DOI：
10.2217/imt-2020-0062
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发表时间：
2020-10
期刊：
影响因子：
2.8
通讯作者：
Liwei Liu;Ming Yang;Qia Xu;Mingzhao Zhou;Yan Cheng;Heming Xu;Yide Qin;Bo Liu
中科院分区：
文献类型：
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作者：
Liwei Liu;Ming Yang;Qia Xu;Mingzhao Zhou;Yan Cheng;Heming Xu;Yide Qin;Bo Liu
目的：探讨程序性死亡1（PD-1）、程序性死亡配体1（PD-L1）、自然杀伤T（NKT）与肝癌细胞共培养体系中的表达，以及去除PD-1对肝癌细胞抗肿瘤效果的影响。材料和方法：分别采用CRISPR/Cas9技术、流式细胞术、ELISA、CCK-8法和小鼠模型研究NKT和肝癌细胞上PD-1/PD-L1表达之间的相互作用。结果：NKT与肝癌细胞相互影响PD-1/PD-L1的表达。NKT对肝癌细胞的杀伤作用与其介导的PD-L1表达呈正相关。结论：不同遗传背景的肝癌细胞对NKT诱导的PD-L1刺激的反应不同，PD-L1表达较低的细胞不能被PD-1阻断干预。此外，PD-1敲除的杀伤效果比单克隆抗体阻断更具有时效性。
Aim: To explore the expression of programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1), natural killer T (NKT) and hepatoma cells in coculture system, and the influence of abolishing PD-1 on antitumor efficiency. Materials & methods: CRISPR/Cas9 technology, flow cytometry, ELISA, CCK-8 assay and mouse models were performed to investigate the interactions between PD-1/PD-L1 expression on NKT and hepatoma cells, respectively. Results: The NKT and hepatoma cells mutually affected the expression of PD-1/PD-L1. The killing effect was positively correlated with NKT-mediated PD-L1 expression on hepatoma cells. Conclusion: Hepatoma cells in different genetic background responded differently to NKT-induced PD-L1 stimulation, and those cells with lower PD-L1 expression fail to PD-1 blocking intervention. Additionally, the killing effect was more time-efficient with PD-1 knockout than with monoclonal antibody blockade.