Grant: Project Grant

Bladder cancer is one of the most common cancers worldwide. It is a very serious cancer because it is not easily cured and it substantially lowers the quality of life of those affected. Most patients with higher-risk bladder cancer are treated with surgery followed by a form of immunotherapy. This immunotherapy involves introducing into the bladder of patients the same bacteria that are used to vaccinate people against tuberculosis (TB). For reasons that we do not fully understand, patients given these bacteria mount an immune response that fights the bladder cancer cells and prevents the cancer from coming back. Unfortunately, up to half of the patients do not respond fully to this therapy, and the cancer comes back. Our research aims to better understand how this immunotherapy of bladder cancer works and, in doing so we also hope to determine why some patients don't respond well to it. Knowing which patients will not respond to this treatment is important because such patients could then be offered an alternative therapy that could potentially save their lives and also spare them from the undesirable side effects of the TB immunotherapy. We have obtained results showing that giving the TB vaccine to bladder cancer patients primes and activates some of the more primitive cells of the immune system. Interestingly, these immune cells are found circulating in the blood of these patients, and their activation appears to occur to a larger extent in cancer patients that respond better to the TB vaccine than in poorly responsive or unresponsive patients. We plan to do experiments to investigate how these 'primed and activated' circulating immune cells can lead to rejection of tumour cells in the bladder. Another potential benefit of our proposed research is that it could lead to the development of new ways to treat bladder cancer patients. It could also help us determine whether similar immunotherapies can be used to treat patients with other types of cancer.