In vitro exposure of normal urothelial cells to IFN-γ similarly induces key immune checkpoint molecules, notably PD-L1 and VISTA, suggesting that immune editing is initiated well before overt neoplastic transformation and may function to limit tissue damage, but under chronic antigenic stimulation, this process can promote a tolerogenic, tumor-permissive microenvironment (28, 37–39). This evidence concerns the gene CD274 and neoplasm.