Grant: Master's Award: Canada Graduate Scholarships

Bcg Immunotherapy; Beta-Glucan; Bladder Cancer; Cytokines; Elisa; Flow Cytometry; Lps; Non-Muscle Invasive Bladder Cancer; Pattern Recognition Receptors; Trained Immunity

"Bladder cancer is the fifth most common cancer in Canada. The most common type is non-muscle invasive bladder cancer (NMIBC), where the patient's tumour is confined to the bladder's mucosa and has not yet invaded into the muscle layer. The standard care of treatment includes the administration of Bacillus Calmette Gu‚rin (BCG) via a urethral catheter. Unfortunately, 40 to 70% of the patients do not respond fully to this treatment resulting in tumour recurrences that can progress to a more advanced disease. Moreover, our understanding of how BCG exerts its anti-tumour effects in NMIBC patients is incomplete. Recently, we have obtained evidence of an association between the response to BCG and trained immunity. Trained immunity (TI) is the acquisition of an immunological memory within innate immune cells and other types of cells such as fibroblasts. This leads me to my hypothesis that bladder tumour cells and healthy urothelial cells contribute to BCG immunotherapy by acquiring a form of TI.. I postulate that tumour and urothelial cells are important for the response to BCG in NMIBC by producing molecules that increase the anti-tumour effects of BCG. To test my hypothesis, I will use tumour and urothelial cells and determine whether they can acquire TI. I will then use a mouse model to study the effects of training on tumour size. <span style=white-space:pre;> Bridging this knowledge gap and understanding the link between trained immunity and the role tumour cells play in BCG treatment may facilitate the development of new therapies such as combination therapies which will help improve patient outcomes and reduce recurrence rates. This knowledge may also help us identify patients who will not respond to BCG treatment and protect them from its side effects. "