Cancer cell-intrinsic mechanisms controlling the immune response to non-muscle-invasive bladder cancer 3077

Abstract Description The majority of urothelial carcinomas are diagnosed as non-muscle-invasive bladder cancer (NMIBC). Standard of care treatment for NMIBC includes tumor resection followed by intravesical administration of bacillus Calmette-Guérin (BCG), a form of immunotherapy. Despite this treatment, nearly 10% of high-risk NMIBC patients will experience progression to muscle-invasive bladder cancer (MIBC) within five years. The factors that determine how a patient responds to BCG are currently unclear. To understand the immune features associated with BCG failure and progression to MIBC, we conducted multiplex immunofluorescence on tumor slides from progressors and non-progressors, both before and after BCG. We analyzed the makeup of the tumor immune microenvironment, including T and B cell subsets, inhibitory cells, and the presence of tertiary lymphoid structures. We then used fluorescence-activated cell sorting to isolate the cancer cells from patient-matched samples and conducted RNA and whole genome sequencing. Using these data, we identified cancer cell phenotypes that are associated with a poor immune response following BCG. These results shed light on the mechanisms of immune evasion in NMIBC and point toward potential new treatment strategies in high-risk patients. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)