Collectively, these prior studies and our current study convincingly show that pharmaceutical blockade of the COX-2/PGE2 axis could become a promising therapeutic approach in bladder cancer (in combination with chemotherapy and ICIs), since blockade of this axis has demonstrated consistent effects in targeting epithelial cancer stem cell repopulation, and reshaping the tumor microenvironment to allow CD8+ T-cell penetration into the tumor core. The gene discussed is CD8A; the disease is urinary bladder cancer.