癌症中 PD-L1 蛋白降解机制和治疗策略的新视野。

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-07-09 DOI:10.1016/j.bbcan.2024.189152
Zhi Li , Xi Yu , Zeting Yuan , Lei Li , Peihao Yin
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引用次数: 0

摘要

程序性死亡配体 1(PD-L1)存在于许多不同的细胞中,因此已成为癌症免疫疗法的一个重要焦点。癌细胞通过提高PD-L1的表达来增强程序性死亡受体1(PD-1)的抑制作用,从而逃避免疫检测。虽然抗PD-1/PD-L1治疗的效果有了明显改善,但仍仅限于特定的患者群体。癌症免疫疗法的一个重要进展是改善了 PD-L1 蛋白的降解。这篇综述深入研究了 PD-L1 的分解过程,包括泛素化-蛋白酶体和自噬-溶酶体等细胞内途径。此外,分析还揭示了影响 PD-L1 稳定性的变化,如磷酸化和糖基化。我们强调了这些过程对癌症免疫疗法的重大影响,以及它们在创新治疗方法中的潜在作用。我们今后的工作重点是了解控制 PD-L1 降解的新方法,并开发创新疗法,如专门设计用于降解 PD-L1 的蛋白水解靶向嵌合体。透彻了解这些途径对于改进癌症免疫疗法策略和提高治疗效果至关重要。
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New horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer

Programmed death-ligand 1 (PD-L1) has become a crucial focus in cancer immunotherapy considering it is found in many different cells. Cancer cells enhance the suppressive impact of programmed death receptor 1 (PD-1) through elevating PD-L1 expression, which allows them to escape immune detection. Although there have been significant improvements, the effectiveness of anti-PD-1/PD-L1 treatment is still limited to a specific group of patients. An important advancement in cancer immunotherapy involves improving the PD-L1 protein degradation. This review thoroughly examined the processes by which PD-L1 breaks down, including the intracellular pathways of ubiquitination-proteasome and autophagy-lysosome. In addition, the analysis revealed changes that affect PD-L1 stability, such as phosphorylation and glycosylation. The significant consequences of these procedures on cancer immunotherapy and their potential role in innovative therapeutic approaches are emphasised. Our future efforts will focus on understanding new ways in which PD-L1 degradation is controlled and developing innovative treatments, such as proteolysis-targeting chimeras designed specifically to degrade PD-L1. It is crucial to have a thorough comprehension of these pathways in order to improve cancer immunotherapy strategies and hopefully improve therapeutic effectiveness.

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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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