ArticleFrontiers in oncology2021
PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- Article
- PD-1 immunology in the kidneys: a growing relationship.Frontiers in immunology · 2024Review
- Prognostic Significance of PD-L2 Expression in Association with Neutrophil-to-Lymphocyte Ratio in Urothelial Carcinoma of the Bladder.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.Frontiers in immunology · 2023Review
- The role of PD-1 signaling in health and immune-related diseases.Frontiers in immunology · 2023Review
- Long Non-Coding RNAs as Epigenetic Regulators of Immune Checkpoints in Cancer Immunity.Cancers · 2022Review
- A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer.Frontiers in cell and developmental biology · 2021Article
- Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of immune checkpoint blockade, in particular PD-1 and PD-L1 inhibitors, is now commonplace in many clinical settings including the treatment of muscle-invasive bladder cancer (MIBC). Notwithstanding, little information exists regarding the expression of the alternative PD-1 ligand, PD-L2 in urothelial bladder cancer (UBC). We therefore set out to characterise the expression of PD-L2 in comparison to PD-L1. Firstly, we assessed PD-L2 expression by immunohistochemistry and found widespread expression of PD-L2 in UBC, albeit with reduced expression in MIBC. We further investigated these findings using RNA-seq data from a cohort of 575 patients demonstrating that PDCD1LG2 (PD-L2) is widely expressed in UBC and correlated with CD274 (PD-L1). However, in contrast to our immunohistochemistry findings, expression was significantly increased in advanced disease. We have also provided detailed evidence of constitutive PD-L2 expression in normal urothelium and propose a mechanism by which PD-L2 is cleaved from the cell surface in MIBC. These data provide a comprehensive assessment of PD-L2 in UBC, showing PD-L2 is abundant in UBC and, importantly, constitutively present in normal urothelium. These data have implications for future development of immune checkpoint blockade, and also the understanding of the function of the immune system in the normal urinary bladder.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.