Grant: Project Grant

Bladder cancer causes close to 20,000 deaths in North America each year. An alarming shift in increased incidence of bladder cancer is being observed in the Canadian population, with approximately 13300 cases in 2022 from ~9000 in 2017 . Being a management intensive and the most expensive to treat cancer, bladder cancer imposes a significant economic burden on health care. Bacillus Calmette-Guerin (BCG) immunotherapy, is the gold standard treatment for the most prevalent form of bladder cancer. More than 50% of patients exhibit either recurrence or progress to an aggressive muscle invasive bladder cancer post BCG therapy. Our novel findings based on evaluation of immune cells from 332 patient tumor specimens, showed that higher number of B cells in pre-treatment tumors associate with early recurrence and poor response to BCG. In the proposed project we aim to define the basis of such negative associations using mouse models, that most closely reflect human disease, and patient derived specimens. We will also develop a novel combination treatment approach to improve response and reduce recurrence and progression, thus sparing patients from bladder removal surgeries. Findings from our study will establish the basis of a novel immunomodulatory treatment strategy for bladder cancer patients. Most importantly, these will rationalize consideration of patient age and sex in the design of improved immunotherapies in adequately powered clinical trials that integrate these factors.