Abstract
Urothelial bladder cancer is the most common malignancy of the urinary tract resulting in over 165,000 deaths worldwide. Immunotherapies targeting the programmed cell death protein-1 (PD-1) checkpoint pathway were recently approved for the treatment of bladder cancer, but favorable responses to this treatment are still limited to a minority of patients. This resistance to therapy has driven a need to optimize syngeneic models of bladder cancer that enable evaluation of the tumor immune microenvironment under varying conditions. Several models have been in place for many years, and we discuss in this chapter the optimization of an orthotopic model of bladder cancer that can be employed to study the anti-tumor immune response.