ArticleThe Journal of clinical investigation2022
BCG therapy downregulates HLA-I on malignant cells to subvert antitumor immune responses in bladder cancer.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 35 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
- Isocyanate-Modified Melatplatin(IV) Enhances Antitumor Efficacy via TCF4/COL6A3-Mediated Extracellular Matrix Remodeling and cGAS-STING Pathway Activation in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circ_0001495 promotes bladder cancer progression by regulating miR-1184 via MAPK signaling pathway.Molecular biology reports · 2026Article
- Combination Strategies to Enhance Bacillus Calmette-Guérin Efficacy for Nonmuscle-Invasive Bladder Cancer.The Journal of urology · 2026Review
- Programmed Cell Death in Urological Cancers: Orchestrating the Immune Microenvironment and Immunotherapy.Oncology research · 2026Review
- Bladder-Preserving Platforms for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.OncoTargets and therapy · 2026Review
- Decoding the temporal dimension of innate immunity in intravesical BCG therapy.Frontiers in immunology · 2026Article
- Article
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Editorial Comment on "Peritumoral Infiltration of Regulatory T Cells Reduces the Therapeutic Efficacy of Bacillus Calmette-Guérin Therapy for Bladder Carcinoma In Situ".International journal of urology : official journal of the Japanese Urological Association · 2025Article
- Review
- [A pan-cancer analysis of PYCR1 and its predictive value for chemotherapy and immunotherapy responses in bladder cancer].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges.Journal of translational medicine · 2025Review
- From Bench to Bladder: The Rise in Immune Checkpoint Inhibition in the Treatment of Non-Muscle Invasive Bladder Cancer.Cancers · 2025Review
- Differential Role of NKG2A/HLA-E Interaction in the Outcomes of Bladder Cancer Patients Treated withBiomedicines · 2025Article
- Tumor cell membrane-based vaccines: A potential boost for cancer immunotherapy.Exploration (Beijing, China) · 2024Review
- Review
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette-Guérin Immunotherapy in Bladder Cancer Patients.International journal of molecular sciences · 2024Article
- The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies.Cell death & disease · 2024Review
Corrections and comments
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Authors and funding
29 authors at 9 institutions in 4 countries.
Funding
Abstract
Patients with high-risk, nonmuscle-invasive bladder cancer (NMIBC) frequently relapse after standard intravesical bacillus Calmette-Guérin (BCG) therapy and may have a dismal outcome. The mechanisms of resistance to such immunotherapy remain poorly understood. Here, using cancer cell lines, freshly resected human bladder tumors, and samples from cohorts of patients with bladder cancer before and after BCG therapy, we demonstrate 2 distinct patterns of immune subversion upon BCG relapse. In the first pattern, intracellular BCG infection of cancer cells induced a posttranscriptional downregulation of HLA-I membrane expression via inhibition of autophagy flux. Patients with HLA-I-deficient cancer cells following BCG therapy had a myeloid immunosuppressive tumor microenvironment (TME) with epithelial-mesenchymal transition (EMT) characteristics and dismal outcomes. Conversely, patients with HLA-I-proficient cancer cells after BCG therapy presented with CD8+ T cell tumor infiltrates, upregulation of inflammatory cytokines, and immune checkpoint-inhibitory molecules. The latter patients had a very favorable outcome. We surmise that HLA-I expression in bladder cancers at relapse following BCG does not result from immunoediting but rather from an immune subversion process directly induced by BCG on cancer cells, which predicts a dismal prognosis. HLA-I scoring of cancer cells by IHC staining can be easily implemented by pathologists in routine practice to stratify future treatment strategies for patients with urothelial cancer.
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Registered trials
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.