Across both BLCA cell lines, IFN-β treatment resulted in a stronger and more sustained phosphorylation of STAT1, a more robust induction of key ISGs like IFIT1, IFIT2, IRF9, MX1, ISG15 and IFI44 a more potent pro-apoptotic effect compared to IFN-α or IFN-λ.IFN-β is the most potent inducer of the upstream interferon signaling cascade (pSTAT1 phosphorylation and ISG expression) in both cell lines tested.The relevance of these findings lies in their direct challenge to the established, IFN-α-centric paradigm in NMIBC therapy. Here, ISG15 is linked to bladder transitional cell carcinoma.