Innate immune memory is associated with increased disease-free survival in bladder cancer patients treated with bacillus Calmette-Guérin
- 4 January 2021
- journal article
- research article
- Published by Canadian Urological Association Journal in Canadian Urological Association Journal
- Vol. 15 (8), E412-E417
- https://doi.org/10.5489/cuaj.7066
Abstract
Introduction: While studies suggest that innate immune memory acquired by circulating monocytes may mediate the benefit of bacillus Calmette-Guérin (BCG) in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC), prospective studies are lacking. Innate immune memory is defined by enhanced release of pro-inflammatory cytokines by innate immune cells following a secondary challenge with pattern recognition receptor (PRR) ligands. Methods: Peripheral blood monocytes isolated from 33 patients with intermediate- or high-risk NMIBC before and after two or five induction BCG instillations were stimulated with the PRR ligand lipopolysaccharide (LPS). Inflammatory cytokine levels in the culture medium were measured. Extent of innate immune memory acquisition was determined by dividing the levels of cytokines released after BCG instillation by the levels released prior to BCG therapy. Results: Monocytes secreted variable levels of TNFα, IL-1β, IL-6, IFNγ, IL-12, and IL-10. Compared with patients with recurrences, the post-BCG:pre-BCG ratio of IL-12 in monocyte cultures from patients without recurrences after five BCG instillations was significantly increased. Patients with no innate immune memory (based on IL-12 ratios) had significantly shorter times-to-recurrence than patients with innate immune memory (pConclusion: Results demonstrate a potential link between BCG-induced innate immune memory peripherally and local anti-tumor responses. Further validation will increase our understanding of the mode of action of BCG and, therefore, will be used to enhance its effectiveness.Keywords
This publication has 17 references indexed in Scilit:
- Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder CancerPLoS Pathogens, 2014
- The mechanism of action of BCG therapy for bladder cancer—a current perspectiveNature Reviews Urology, 2014
- Strategies for Optimizing Bacillus Calmette-GuérinUrologic Clinics of North America, 2013
- Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytesProceedings of the National Academy of Sciences of the United States of America, 2012
- Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder CancerScience Translational Medicine, 2012
- Mycobacterium bovisBacillus Calmette-Guérin-Induced Macrophage Cytotoxicity against Bladder Cancer CellsJournal of Immunology Research, 2010
- A possible mechanism of intravesical BCG therapy for human bladder carcinoma: involvement of innate effector cells for the inhibition of tumor growthCancer Immunology, Immunotherapy, 2009
- Role of Th1-stimulating cytokines in bacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cellsClinical and Experimental Immunology, 2006
- Neutrophil Granulocytes Are Required for EffectiveBacillus Calmette-GuérinImmunotherapy of Bladder Cancer and Orchestrate Local Immune ResponsesCancer Research, 2006
- Management of BCG Failures in Superficial Bladder Cancer: A ReviewEuropean Urology, 2006