Innate immune memory is associated with increased disease-free survival in bladder cancer patients treated with bacillus Calmette-Guérin
Autor: | Charles C.T. Hindmarch, Jean-François Paré, Madhuri Koti, Diana Marginean, Wilma M. Hopman, D. Robert Siemens, Abdi Ghaffari, Charles H. Graham, Tiziana Cotechini, Stephen Chenard |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Bladder cancer Innate immune system Lipopolysaccharide business.industry Urology medicine.medical_treatment Monocyte Pattern recognition receptor medicine.disease 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Cytokine medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis Immunology medicine Tumor necrosis factor alpha business Prospective cohort study |
Zdroj: | Canadian Urological Association Journal. 15 |
ISSN: | 1920-1214 1911-6470 |
Popis: | 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 (p |
Databáze: | OpenAIRE |
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