Observational studyJournal for immunotherapy of cancer2023
Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.
Observational study in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.Immunology letters · 2024Trial
- Molecular Classifications and Candidate Biomarkers for Personalizing BCG Therapy in Non-Muscle-Invasive Bladder Cancer.Biomedicines · 2026Review
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
- Monocyte/macrophage-mediated trained immunity in disease prevention and immunotherapy.Bioactive materials · 2026Review
- Tissue context as a determinant of trained innate immunity: a conserved molecular toolkit with divergent functional outputs.Journal of leukocyte biology · 2026Review
- BLOSSOM Dietary Habits and 1-Year Intravesical Recurrence in High-Risk Non-Muscle-Invasive Bladder Cancer Treated with BCG.Current oncology (Toronto, Ont.) · 2026Article
- Bladder-Preserving Platforms for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.OncoTargets and therapy · 2026Review
- The TRIM-cancer paradox: BCG as a programmable vaccine platform and a mechanistic probe for rational immunotherapy design.Frontiers in immunology · 2026Review
- Heat-killedFrontiers in immunology · 2026Article
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- Review
- Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven anti-tumor immunity.Cancer cell · 2025Article
- Training the synergy between Bacillus Calmette-Guérin and immune checkpoint-blocking antibodies in bladder cancer.Cancer communications (London, England) · 2025Article
- Development of Novel Intravesical Formulation for Bladder Retention Targeting Bladder Disorders.Current drug targets · 2025Review
- Recent Advances of Trained immunity in Macrophages.International journal of biological sciences · 2025Review
- Induction of trained immunity in myeloid cells and their progenitors from thyroid cancer patients.Frontiers in immunology · 2025Article
- Enhanced Immune Responses AgainstIndian journal of microbiology · 2024Article
- Multifaceted roles of trained immunity in diverse pathological contexts.BMB reports · 2024Review
- Review
- Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.Epigenomics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundBCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.
methodsThe aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response.
resultsWe found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex vivo stimulation of circulating monocytes 6-12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.
conclusionWe conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients.
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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.