Bladder cancer is the fourth most common cancer among men in the United States. While low-grade tumors have a very favorable prognosis, muscle-invasive and metastatic tumors have poorer survival rates. In this month's issue of JCI Insight, William Kim, Benjamin Vincent, and a research team from the University of North Carolina characterized a new subtype of muscle-invasive bladder cancer that shares molecular signatures with some forms of breast cancer. A subset of triple-negative breast cancers express low levels of the tight junction protein claudin. The UNC researchers now document that claudin-low tumors represent a specific subtype of bladder cancer as well. Using data from the The Cancer Genome Atlas (TCGA) urothelial bladder carcinoma data set, they found that claudin-low tumors express high levels of immune-related genes, but also show a strong signature of immunosuppression. These finding suggest that claudin-low bladder cancers may be particularly responsive to immunotherapy-based treatments that derepress the immune system. Future studies will be needed to clinically test immune checkpoint inhibitors in this population.