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

Sep 21, 2026

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Programmed death receptor-1 (PD-1) and its ligand PD-L1 are key regulators of immune responses. PD-L1 is constitutively present on immune cells, epithelial cells, and cancer cells, acting as a co-stimulatory molecule that can impair T-cell–mediated immunity. Engagement of PD-1 on activated T cells activates signaling that promotes apoptosis or anergy, enabling tumor immune escape. In urological cancers, PD-L1 upregulation correlates with poor prognosis and enhanced evasion. The review summarizes the regulatory mechanisms controlling PD-1/PD-L1 expression and activity, discusses PD-1/PD-L1 checkpoint inhibitor research, and analyzes resistance challenges to improve immunotherapy efficacy.

LanguageEnglish

CategoryHealthcare

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Pages26

Reading Time1 h 6 min

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Abstract

Overview of PD-1/PD-L1 signaling in urological cancers

Clinical applications of PD-1/PD-L1 inhibitors and resistance challenges

Regulatory mechanisms of PD-1/PD-L1 expression and activity

Liu et al. Molecular Cancer (2024) 23:183 Molecular Cancer [https://doi.org/10.1186/s12943-024-02095-8](https://doi.org/10.1186/s12943-024-02095-8) REVIEW Open Access Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy Qiang Liu 1, Yujing Guan2,3,4 and Shenglong Li2,3,4* 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. The original online version of this article was revised: Following publication of the original article [1], the author reported that the published PDF version is incorrect as the information such as"(See Fig. 5)", "(Fig. 4; Table 3)", and "[170]" need to be removed and updated accordingly as shown in the correction article [https://doi](https://doi). org/10 . 1186/s12943-024-02121-9 . *Correspondence: Shenglong Li [slli@cmu.edu.cn](slli@cmu.edu.cn); [lishenglong@dl ut.edu.cn](lishenglong@dl ut.edu.cn); [lishenglong@cancerhosp-ln-cmu.com](lishenglong@cancerhosp-ln-cmu.com) Full list of author information is available at the end of the article © The Author(s) 2024, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[cr

FAQs

What role do PD-1 and PD-L1 play in immune regulation?

PD-1 and PD-L1 are essential molecules that modulate immune responses. PD-L1 can impair T-cell–mediated immunity and, through PD-1 binding, contribute to T-cell apoptosis or anergy.

How does PD-1/PD-L1 signaling contribute to immune escape in urological cancers?

In urological cancers such as bladder cancer, renal cell carcinoma, and prostate cancer, PD-L1 upregulation supports immune evasion. It contributes to immunosuppression by inhibiting T-cell activation and proliferation.

Why are PD-1/PD-L1 checkpoint inhibitors challenging in treating advanced urological cancers?

Although checkpoint inhibitors show promising efficacy, resistance remains a major problem. Resistance can be intrinsic or acquired, reducing long-term effectiveness.

Sep 21, 2026

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