Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-09-02 DOI:10.1186/s12943-024-02095-8

Qiang Liu, Yujing Guan, Shenglong Li

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引用次数: 0

Abstract

Programmed death receptor-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1) are essential molecules that are key in modulating immune responses. PD-L1 is constitutively expressed on various immune cells, epithelial cells, and cancer cells, where it functions as a co-stimulatory molecule capable of impairing T-cell mediated immune responses. Upon binding to PD-1 on activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways that can induce T-cell apoptosis or anergy, thereby facilitating the immune escape of tumors. In urological cancers, including bladder cancer (BCa), renal cell carcinoma (RCC), and prostate cancer (PCa), the upregulation of PD-L1 has been demonstrated. It is linked to poor prognosis and enhanced tumor immune evasion. Recent studies have highlighted the significant role of the PD-1/PD-L1 axis in the immune escape mechanisms of urological cancers. The interaction between PD-L1 and PD-1 on T-cells further contributes to immunosuppression by inhibiting T-cell activation and proliferation. Clinical applications of PD-1/PD-L1 checkpoint inhibitors have shown promising efficacy in treating advanced urological cancers, significantly improving patient outcomes. However, resistance to these therapies, either intrinsic or acquired, remains a significant challenge. This review aims to provide a comprehensive overview of the role of the PD-1/PD-L1 signaling pathway in urological cancers. We summarize the regulatory mechanism underlying PD-1 and PD-L1 expression and activity, including genetic, epigenetic, post-transcriptional, and post-translational modifications. Additionally, we discuss current clinical research on PD-1/PD-L1 inhibitors, their therapeutic potential, and the challenges associated with resistance. Understanding these mechanisms is crucial for developing new strategies to overcome therapeutic limitations and enhance the efficacy of cancer immunotherapy.

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泌尿系统癌症中的程序性死亡受体（PD-）1/PD-配体（L）1：免疫疗法中的 "全能战士

程序性死亡受体-1（PD-1）及其配体程序性死亡配体-1（PD-L1）是调节免疫反应的重要分子。PD-L1 在各种免疫细胞、上皮细胞和癌细胞上都有表达，它是一种协同刺激分子，能够损害 T 细胞介导的免疫反应。与活化 T 细胞上的 PD-1 结合后，PD-1/PD-L1 相互作用会触发信号通路，诱导 T 细胞凋亡或失活，从而促进肿瘤的免疫逃逸。在膀胱癌（BCa）、肾细胞癌（RCC）和前列腺癌（PCa）等泌尿系统癌症中，PD-L1 的上调已得到证实。这与预后不良和肿瘤免疫逃避能力增强有关。最近的研究强调了 PD-1/PD-L1 轴在泌尿系统癌症免疫逃避机制中的重要作用。T 细胞上的 PD-L1 和 PD-1 之间的相互作用通过抑制 T 细胞的活化和增殖进一步促进了免疫抑制。PD-1/PD-L1 检查点抑制剂的临床应用已显示出治疗晚期泌尿系统癌症的良好疗效，显著改善了患者的预后。然而，这些疗法的耐药性，无论是内在的还是后天获得的，仍然是一个重大挑战。本综述旨在全面概述 PD-1/PD-L1 信号通路在泌尿系统癌症中的作用。我们总结了 PD-1 和 PD-L1 表达和活性的调控机制，包括遗传、表观遗传、转录后和翻译后修饰。此外，我们还讨论了目前有关 PD-1/PD-L1 抑制剂的临床研究、其治疗潜力以及与耐药性相关的挑战。了解这些机制对于开发新的策略以克服治疗限制和提高癌症免疫疗法的疗效至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.