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PD-L1 的核转运及其在肿瘤免疫与进展中的功能

英文原题:The nuclear transportation of PD-L1 and the function in tumor immunity and progression.

查看英文原题

The nuclear transportation of PD-L1 and the function in tumor immunity and progression.

PubMed 2022/03/05(内容时间) Cancer Immunol Immunother Q1 · IF 5.8(JCR 2025)

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中文摘要

作为主要的免疫检查点,PD-L1-PD-1相互作用在效应T细胞失调中发挥关键作用,这导致了CAR-T 细胞及其他免疫治疗的失败。目前,大多数研究聚焦于PD-L1的细胞外功能。膜PD-L1可与其受体PD-1相互作用,降低T细胞诱导的肿瘤免疫。然而,PD-L1在癌细胞中的功能仍不清楚。近期研究表明,PD-L1表达在不同癌症类型中具有不同的临床意义,显示了PD-L1在癌细胞调控中的复杂性。作为一种新的调控途径,癌细胞中PD-L1的核转位受到更多关注。这些临床前研究的结果表明,核PD-L1在癌症发展及其他免疫检查点分子转录中具有重要作用。在此,我们总结了PD-L1核转运所涉及的机制,并确定了该过程中的关键调控因子。此外,我们还总结了核PD-L1在癌症免疫中的功能。这些发现提示了PD-L1在癌症发展中的新调控机制,表明核PD-L1是未来癌症治疗中潜在的治疗靶点。

展开英文摘要原文

As the main immune checkpoint, PD-L1-PD-1 interaction plays a critical role in the dysregulation of effector T cells, which contributes to the failure of Chimeric Antigen Receptor T-cell (CAR-T) and other immunotherapies. Presently, most research focuses on the extracellular function of PD-L1. Membrane PD-L1 can interact with its receptor PD-1 and decrease T cell-induced cancer immunity.

However, the function of PD-L1 in cancer cells is still unclear. Recent studies have shown the separated clinical significance of PD-L1 expression in various cancer types, showing the complexity of PD-L1 in cancer cell regulation. As a novel regulatory pathway, the nuclear translocation of PD-L1 in cancer cells receives more attention. Results of these preclinical studies demonstrated that nuclear PD-L1 has an essential role in cancer development and other immune checkpoint molecules transcription.

Herein, we summarized the mechanisms involved in PD-L1 nuclear transportation and identify the key regulatory factors in this process.

Furthermore, we also summarize the function of nuclear PD-L1 in cancer immunity.

These findings suggested the novel PD-L1 regulation in cancer development, which showed that nuclear PD-L1 is a potential therapeutic target in future cancer therapy.

论文信息

作者
Qu L、Jin J、Lou J、Qian C、Lin J、Xu A、Liu B、Zhang M
第一作者单位
Clinical Laboratory Centre, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China.China
通讯作者单位
Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009, Zhejiang, People's Republic of China. 11818244@zju.edu.cn.China
文献类型
综述
期刊
Cancer immunology, immunotherapy : CII2022 Oct
原文标识
PubMed 35246703 · DOI 10.1007/s00262-022-03176-7