CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The nuclear transportation of PD-L1 and the function in tumor immunity and progression.
The nuclear transportation of PD-L1 and the function in tumor immunity and progression.
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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。
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.
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