Department of Respiratory Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Hospice Care, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.
Front Immunol. 2024 Apr 4;15:1392546. doi: 10.3389/fimmu.2024.1392546. eCollection 2024.
Immunotherapy has been developed, which harnesses and enhances the innate powers of the immune system to fight disease, particularly cancer. PD-1 (programmed death-1) and PD-L1 (programmed death ligand-1) are key components in the regulation of the immune system, particularly in the context of cancer immunotherapy. PD-1 and PD-L1 are regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation and glycosylation. PROTACs (Proteolysis Targeting Chimeras) are a type of new drug design technology. They are specifically engineered molecules that target specific proteins within a cell for degradation. PROTACs have been designed and demonstrated their inhibitory activity against the PD-1/PD-L1 pathway, and showed their ability to degrade PD-1/PD-L1 proteins. In this review, we describe how PROTACs target PD-1 and PD-L1 proteins to improve the efficacy of immunotherapy. PROTACs could be a novel strategy to combine with radiotherapy, chemotherapy and immunotherapy for cancer patients.
免疫疗法已经发展起来，它利用和增强免疫系统的固有能力来对抗疾病，特别是癌症。PD-1（程序性死亡受体 1）和 PD-L1（程序性死亡配体 1）是免疫系统调节的关键组成部分，特别是在癌症免疫治疗的背景下。PD-1 和 PD-L1 受到 PTMs 的调节，包括磷酸化、泛素化、去泛素化、乙酰化、棕榈酰化和糖基化。PROTACs（蛋白水解靶向嵌合体）是一种新型药物设计技术。它们是专门设计的分子，可以针对细胞内的特定蛋白质进行降解。已经设计了 PROTACs 并证明了它们对 PD-1/PD-L1 通路的抑制活性，并显示了它们降解 PD-1/PD-L1 蛋白的能力。在这篇综述中，我们描述了 PROTACs 如何靶向 PD-1 和 PD-L1 蛋白以提高免疫疗法的疗效。PROTACs 可能是一种将放射治疗、化学疗法和免疫疗法相结合的新策略，适用于癌症患者。
