ArticleClinical and experimental immunology2006
Role of Th1-stimulating cytokines in bacillus Calmette-Guérin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells.
Article in Clinical and experimental immunology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 74 citations in OpenAlex.
- Immunomodulatory effects of total intravenous and balanced inhalation anesthesia in patients with bladder cancer undergoing elective radical cystectomy: preliminary results.Journal of experimental & clinical cancer research : CR · 2013Trial
- The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial.Journal of translational medicine · 2010Trial
- Immunotherapy role in bladder cancer treatment: a review of literature.Frontiers in oncology · 2026Review
- Differential effects of BCG-Russia and BCG-TICE on trained immunity: Potential implications for bladder cancer immunotherapy.PloS one · 2026Article
- Synthesis and Evaluation of Trehalose-Based Mertansine Warheads for Bacillus Calmette-Guérin Delivery of Anticancer Agents.Chembiochem : a European journal of chemical biology · 2025Article
- Review of BCG immunotherapy for bladder cancer.Clinical microbiology reviews · 2025Review
- Functional roles and cancer variants of the bifunctional glycosylase NEIL2.Environmental and molecular mutagenesis · 2024Review
- Immune Predictors of Response after BacillusCancers · 2023Review
- The androgen receptor in bladder cancer.Nature reviews. Urology · 2023Review
- Highlights into historical and current immune interventions for cancer.International immunopharmacology · 2023Review
- Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections.Journal for immunotherapy of cancer · 2023Observational
- Detailed Structural Analysis of the Immunoregulatory Polysaccharides from the Mycobacterium Bovis BCG.Molecules (Basel, Switzerland) · 2022Article
- Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo withBiomedicines · 2021Article
- Review
- Innate immune memory is associated with increased disease-free survival in bladder cancer patients treated with bacillus Calmette-Guérin.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2021Article
- The multifaceted immune regulation of bladder cancer.Nature reviews. Urology · 2019Review
- Macrophage polarization as a novel weapon in conditioning tumor microenvironment for bladder cancer: can we turn demons into gods?Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.PLoS neglected tropical diseases · 2017Article
- Toll-Like Receptor Ligands and Interferon-γ Synergize for Induction of Antitumor M1 Macrophages.Frontiers in immunology · 2017Article
- Periductal Mastitis: An Inflammatory Disease Related to Bacterial Infection and Consequent Immune Responses?Mediators of inflammation · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Previously, we have demonstrated that macrophages exhibited cytotoxicity toward mouse bladder cancer MBT-2 cells upon bacille Calmette-Guérin (BCG) stimulation. In this study, we have investigated the role of Th1-stimulating cytokines in BCG-induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells (PECs) were used as a conventional source for macrophages and the induction of PEC effector functions (cytolytic activity and cytokine production) by BCG was evaluated in vitro. The BCG-activated PECs showed potent cytotoxicity and killed MBT-2 cells in a dose-dependent manner. Depletion of T cells, natural killer (NK) cells, or both, in PEC preparations exhibited a marginal or small reduction of MBT-2 cell killing, suggesting that macrophages played a primary role in PEC cytotoxicity. Transwell assays indicated that the maximal PEC cytotoxicity required both direct cell-cell contact and soluble factors such as interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Neutralizing endogenous cytokines interleukin (IL)-12, IL-18, IFN-gamma or TNF-alpha reduced PEC cytotoxicity by 38%, 22%, 15% and 94%, respectively. Supplementation of BCG with recombinant (r)IL-2, rIL-12 or rIL-18 increased PEC cytotoxicity by approximately twofold. Compared with control BCG for PEC stimulation, rBCGs expressing IL-2 or IL-18 showed enhanced MBT-2 cell killing by PECs. Increased cytokine production (IFN-gamma, TNF-alpha and IL-6) was also observed in rBCG-stimulated PEC cultures. Taken together, these results suggest that Th1-stimulating cytokines play an important role in BCG-induced macrophage cytotoxicity and that combination of BCG with selected Th1-stimulating cytokines, either supplemented or expressed by BCG, may enhance the effect of BCG in the treatment of bladder cancer patients.
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