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UCHL1 promotes expression of PD-L1 in non-small cell lung cancer cells.

UCHL1 促进非小细胞肺癌细胞 PD-L1 表达

  • 影响因子:4.60
  • DOI:10.1111/cas.14529
  • 作者列表:"Mao R","Tan X","Xiao Y","Wang X","Wei Z","Wang J","Wang X","Zhou H","Zhang L","Shi Y
  • 发表时间:2020-06-15
Abstract

:PD-L1 expressed on the cancer cells can cause immune escape of NSCLC. Elucidation of the regulatory mechanisms of the PD-L1 expression is a prerequisite for establishment of new tumor immunotherapy strategies. Deubiquitinase UCHL1 is a regulator of cellular signaling transduction and expressed aberrantly in NSCLC. But it is not known whether UCHL1 regulates the expression of PD-L1 in NSCLC cells. In the present study, we found that UCHL1 promotes the expression of PD-L1 in NSCLC cell lines. Besides, UCHL1 expressed in NSCLC cells inhibited activation of Jurkat cells through upregulation of PD-L1 expression in vitro experiments. Moreover, the mechanism for UCHL1 to upregulate PD-L1 expression is that UCHL1 facilitated activation of AKT-P65 signaling pathway. In conclusion, these results demonstrated that UCHL1 promoted PD-L1 expression in NSCLC cells. This finding implied that inhibition of UCHL1 might suppress immune escape of NSCLC via downregulation of PD-L1 expression in NSCLC cells.

摘要

: PD-L1 在癌细胞上的表达可引起 NSCLC 的免疫逃逸。阐明 PD-L1 的表达调控机制是建立新的肿瘤免疫治疗策略的前提。去泛素化酶 UCHL1 是细胞信号转导的调节因子,在 NSCLC 中表达异常。但 UCHL1 是否调控 NSCLC 细胞 PD-L1 的表达尚不清楚。在本研究中,我们发现 UCHL1 促进 NSCLC 细胞系中 PD-L1 的表达。此外,在体外实验中,NSCLC 细胞表达的 UCHL1 通过上调 PD-L1 的表达抑制 Jurkat 细胞的活化。此外,UCHL1 上调 PD-L1 表达的机制是 UCHL1 促进了 AKT-P65 信号通路的激活。总之,这些结果证明 UCHL1 促进 NSCLC 细胞 PD-L1 表达。这一发现意味着抑制 UCHL1 可能通过下调 NSCLC 细胞中 PD-L1 的表达来抑制 NSCLC 的免疫逃逸。

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