PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders.

IF 12.1 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Molecular Therapy Pub Date : 2024-12-04 Epub Date: 2024-09-28 DOI:10.1016/j.ymthe.2024.09.026
Daeun Lee, Minjeong Cho, Eunseo Kim, Youngbin Seo, Jong-Ho Cha
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Abstract

The PD-L1/PD-1 signaling pathway is the gold standard for cancer immunotherapy. Therapeutic antibodies targeting PD-1, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), and PD-L1, including atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) have received Food and Drug Administration approval and are currently being used to treat various cancers. Traditionally, PD-L1 is known as an immune checkpoint protein that binds to the PD-1 receptor on its surface to inhibit the activity of T cells, which are the primary effector cells in antitumor immunity. However, it also plays a role in cancer progression, which goes beyond traditional understanding. Here, we highlight the multifaceted mechanisms of action of PD-L1 in cancer cell proliferation, transcriptional regulation, and systemic immune suppression. Moreover, we consider the potential role of PD-L1 in the development and pathogenesis of diseases other than cancer, explore PD-L1-focused therapeutic approaches for these diseases, and assess their clinical relevance. Through this review, we hope to provide deeper insights into the PD-L1/PD-1 signaling pathway and present a broad perspective on potential therapeutic approaches for cancer and other diseases.

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PD-L1:从癌症免疫疗法到多种疾病的治疗意义。
PD-L1/PD-1 信号通路是癌症免疫疗法的黄金标准。针对 PD-1 的治疗性抗体,如 nivolumab (Opdivo) 和 pembrolizumab (Keytruda),以及针对 PD-L1 的治疗性抗体,包括 atezolizumab (Tecentriq)、durvalumab (Imfinzi) 和 avelumab (Bavencio),均已获得 FDA 批准,目前正用于治疗各种癌症。传统上,PD-L1 被认为是一种免疫检查点蛋白,它能与其表面的 PD-1 受体结合,抑制 T 细胞的活性,而 T 细胞是抗肿瘤免疫的主要效应细胞。然而,它在癌症进展中也发挥着作用,这超出了人们的传统认识。在此,我们将重点介绍 PD-L1 在癌细胞增殖、转录调控和全身免疫抑制中的多方面作用机制。此外,我们还考虑了 PD-L1 在癌症以外的其他疾病的发展和发病机制中的潜在作用,探讨了针对这些疾病的 PD-L1 治疗方法,并评估了这些方法的临床意义。我们希望通过这篇综述深入了解 PD-L1/PD-1 信号通路,并从广阔的视角探讨癌症和其他疾病的潜在治疗方法。
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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
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