Grant: Operating Grant

Bladder cancer is sixth in incidence in Canada. About 75% of initial tumors are non-muscle invasive and although treated effectively by transurethral surgery, will recur in 50-80% of cases and progress to invasive cancer in 10-20% of patients. The preferred treatment to prevent recurrence and progression of high-risk tumors is non-specific immunotherapy with bacillus Calmette-Guérin (BCG). The efficacy of BCG immunotherapy thus offers a unique model and opportunity to investigate the immune response in cancer. Data in the literature have identified a gene that is involved in resistance to BCG therapy for bladder cancer in mice. In humans, that same gene has been linked to susceptibility to various infectious and autoimmune diseases. It is known to be involved in immunity. We obtained evidence that alteration of this gene can affect the response to BCG. We also observed its expression in normal bladder and in some bladder tumors. Moreover we observed a statistically significant correlation between the presence of different cells of the immune system infiltrating bladder tumors and the response of patients to BCG treatment. These cells of the immune system are known to express that same gene, which thus appears to be a central actor in the immune response to tumors. In this project, we plan to further pursue the characterization of the identified gene in bladder cancer to better understand its role in resistance to immunotherapy. This will be realized by using normal and tumoral bladder cells, that will be grown in the lab and submitted to BCG or similar therapies. The effect of BCG and alternate immunotherapies will be analyzed by measuring the modulation of a series of genes related to the immune response. We will also pursue the analysis of infiltration of cells of the immune system in bladder tumors and of characteristics of bladder tumor cells in correlation with the response of tumors to immunotherapy.