Fangni Chai, Pan Li, Xin Liu, Zhihui Zhou, Haiyan Ren
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引用次数: 0
摘要
程序性细胞死亡1配体1 (programmed cell death 1 ligand 1, PD-L1)作为免疫检查点的重要成员,在肿瘤免疫逃逸中起着至关重要的作用,已成为肿瘤免疫治疗的重要靶点。临床批准的药物主要靶向PD-L1的细胞外结构域。最近,PD-L1的小细胞质结构域被报道通过多种途径调节PD-L1的稳定性和功能。因此,PD-L1的细胞内结构域及其调控途径可能是癌症治疗的有希望的靶点,扩大了联合免疫治疗的可用策略。在这里,我们总结了PD-L1细胞质结构域及其调控途径的新作用。据报道,PD-L1细胞质结构域的保守基序、同二聚化和翻译后修饰可调节PD-L1的膜锚定、降解、核易位和糖基化等。这篇综述提供了对PD-L1细胞质结构域功能的全面了解,并评估了靶向治疗的广阔前景。
Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy.
As a significant member of the immune checkpoint, programmed cell death 1 ligand 1 (PD-L1) plays a critical role in cancer immune escape and has become an important target for cancer immunotherapy. Clinically approved drugs mainly target the extracellular domain of PD-L1. Recently, the small cytoplasmic domain of PD-L1 has been reported to regulate PD-L1 stability and function through multiple pathways. Therefore, the intracellular domain of PD-L1 and its regulatory pathways could be promising targets for cancer therapy, expanding available strategies for combined immunotherapy. Here, we summarize the emerging roles of the PD-L1 cytoplasmic domain and its regulatory pathways. The conserved motifs, homodimerization, and posttranslational modifications of the PD-L1 cytoplasmic domain have been reported to regulate the membrane anchoring, degradation, nuclear translocation, and glycosylation of PD-L1. This summary provides a comprehensive understanding of the functions of the PD-L1 cytoplasmic domain and evaluates the broad prospects for targeted therapy.
期刊介绍:
The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome.
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