Effects of Prophylactic β-glucan Administration Against Non-Muscle Invasive Urinary Bladder Cancer
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Authors
Butterfield, Andrew Jack
Date
2025-01-31
Type
project
Language
en
Keyword
Alternative Title
Abstract
Introduction: Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. The gold-standard treatment is transurethral resection of bladder tumour (TURBT) followed by intravesical administration of Bacillus Calmette-Guérin (BCG), but this treatment is associated with significant limitations including a high recurrence rate and high rate of adverse effects. While the therapeutic mode of BCG is not fully known, there is evidence that BCG-mediated systemic acquisition of trained immunity may play a role. This thesis examined the role of β-glucan, an immunogenic polysaccharide, as a potential alternative treatment for NMIBC. Like BCG, β-glucan has also been demonstrated to induce epigenetic changes characteristic of trained immunity, but unlike BCG, β-glucan is not a live bacterium, and thus may be associated with a reduced likelihood of adverse effects.
Hypothesis: Systemic administration of β-glucan is effective against bladder cancer.
Materials & Methods: Two groups of C57BL/6 mice were pretreated intraperitoneally with β-glucan or PBS twice prior to intravesical instillation of MB49-Luc cells, a murine urothelial carcinoma cell line transfected with luciferase. To assess tumour growth, in vivo bioluminescence imaging was used. Mice were euthanized 10 days after tumour cell instillation; bladders and tumour-draining lymph nodes (tdLNs) were collected and subjected to flow cytometry. Analysis of tumour growth was repeated in a separate experiment. Mice following the same dosing protocol were subjected to lipopolysaccharide (LPS) stimulation 6 days after β-glucan administration, followed by euthanasia and blood collection 4 hours later. Cytokine concentrations in the collected blood were analyzed.
Results: A significant reduction in overall tumour burden was noted in the repeated experiment assessing tumour growth, as was a significant reduction in initial tumour growth. This inhibition of tumour growth was associated with a significant increase in Interleukin-12p70 (IL-12p70) in a separate cohort of β-glucan-treated mice. Proportions of several immune cells were significantly altered in the tdLNs of β-glucan treated mice.
Conclusions: Overall, results point to a therapeutic benefit of β-glucan in the treatment/prevention of bladder cancer. Given the discrepancy in the findings of the tumour growth experiments, additional studies are warranted. Evidence of acquisition of trained immunity following β-glucan administration further supports the concept that the therapeutic benefit of β-glucan may be mediated by trained immunity; however, mechanistic studies are needed to establish causality.