ArticleEuropean urology2022
Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with Bacillus Calmette-Guérin Failure in Patients with Non-muscle-invasive Bladder Cancer.
Article in European urology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Urine cell-free RNA for bladder cancer detection and treatment response prediction.Nature medicine · 2026Article
- Molecular Classifications and Candidate Biomarkers for Personalizing BCG Therapy in Non-Muscle-Invasive Bladder Cancer.Biomedicines · 2026Review
- Urinary Biomarkers in Urological Oncology: From Biological Origin to Clinical Decision-Making-A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- Impact of Photodynamic Diagnosis on Immune Cell Infiltration in BCG-treated Non-muscle-invasive Bladder Cancer.European urology open science · 2026Article
- Unveiling the Paradoxical Tumor-Suppressive Role of CCL2/CCR2 in Bladder Cancer: A Novel Immunotherapeutic Strategy.Cancers · 2026Article
- Evaluation of human epidermal growth factor receptor 2 (HER2)-related genes revealed that HER2-antibody-drug conjugate (ADC) drugs confer clinical benefits to Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer patients.Translational andrology and urology · 2026Article
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- The changing landscape of urothelial carcinoma: on the edge of a paradigm shift.The Journal of clinical investigation · 2026Review
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- Article
- The cost of persistent alarm: temporal transcriptional reprogramming of macrophages from acute activation to chronic immune suppression by day 11.Frontiers in immunology · 2026Article
- ERBB2 mutations promote recurrence and metastasis in non-muscle-invasive bladder cancer via HIF-1 phosphorylation: Insights from whole exome sequencing.Journal of pharmaceutical analysis · 2026Article
- Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer.Oncoimmunology · 2025Article
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- T cell subsets of urine-derived lymphocytes (UDLs) serve as an indicator of TILs and reflect immunological sex differences in bladder cancer.Journal for immunotherapy of cancer · 2025Article
- Single-cell RNA-sequencing of BCG naïve and recurrent non-muscle invasive bladder cancer reveals a CD6/ALCAM-mediated immune-suppressive pathway.NPJ precision oncology · 2025Article
- HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.bioRxiv : the preprint server for biology · 2025Article
- Circulating tumour DNA and circulating tumour cells in bladder cancer - from discovery to clinical implementation.Nature reviews. Urology · 2025Review
- Blocking secretion of exosomes by GW4869 dampens CD8Human cell · 2025Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe functional status of immune cells in the tumor microenvironment and tumor characteristics may explain bacillus Calmette-Guérin (BCG) failure in high-risk non-muscle-invasive bladder cancer (NMIBC).
objectiveTo characterize molecular correlates of post-BCG high-grade (HG) recurrence using multiomics analysis. DESIGN, SETTING, AND
participantsPatients with BCG-treated NMIBC (n = 156) were included in the study. Metachronous tumors were analyzed using RNA sequencing (n = 170) and whole-exome sequencing (n = 195). Urine samples were analyzed for immuno-oncology-related proteins (n = 190) and tumor-derived DNA (tdDNA; n = 187). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was post-BCG HG recurrence. Cox regression and Wilcoxon rank-sum, t, and Fisher's exact tests were used for analyses. RESULTS AND LIMITATIONS: BCG induced activation of the immune system regardless of clinical response; however, immunoinhibitory proteins were observed in the urine of patients with post-BCG HG recurrence (CD70, PD1, CD5). Post-BCG HG recurrence was associated with post-BCG T-cell exhaustion (p = 0.002). Pre-BCG tumors from patients with post-BCG T-cell exhaustion had high expression of genes related to cell division and immune function. A high predicted post-BCG exhaustion score for pre-BCG tumors was associated with worse post-BCG HG recurrence-free survival (HGRFS; p = 0.002). This was validated in independent cohorts. Pre-BCG class 2a and 2b tumors (UROMOL2021 scheme) were associated with worse post-BCG HGRFS (p = 0.015). Post-BCG exhaustion was observed in patients with high pre-BCG neoantigen load (p = 0.017) and MUC4 mutations (p = 0.002). Finally, the absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (p = 0.018). The retrospective design and partial overlap for analyses are study limitations.
conclusionsPost-BCG HG recurrence may be caused by T-cell exhaustion. Tumor subtype and pre-BCG tumor characteristics may identify patients at high risk of post-BCG HG recurrence. Urinary measurements have potential for real-time assessment of treatment response. PATIENT SUMMARY: A dysfunctional immune response to bacillus Calmette-Guérin (BCG) therapy may explain high-grade recurrences of bladder cancer.
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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.