Recent advances and mechanisms of action of PD-L1 degraders as potential therapeutic agents

PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new op...

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Veröffentlicht in:European journal of medicinal chemistry 2024-03, Vol.268, p.116267-116267, Article 116267
Hauptverfasser: Zhang, Feng, Jiang, Ruiya, Sun, Shishi, Wu, Caiyun, Yu, Qimeng, Awadasseid, Annoor, Wang, Jianwei, Zhang, Wen
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Sprache:eng
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Zusammenfassung:PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new opportunities for immunotherapy. Here, we mainly summarize and review the current active molecules and mechanisms that mediate the degradation of immature and mature PD-L1 during the post-translational modification stages, involving PD-L1 phosphorylation, glycosylation, palmitoylation, ubiquitination, and the autophagy-lysosomal process. This review expects that by degrading PD-L1 protein, we will not only gain a better understanding of oncogenic mechanisms involving tumor PD-L1 protein but also provide a new way to improve immunotherapy. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2024.116267