In this work it was shown that EHMT2 (or G9a) expression associated with poor outcome in BlCa and that targeting both EHMT2 and DNA methyltransferase (DNMT) activity (inhibitor CM-272) significantly enhances antitumor effects, that is potentiated when combining with anti-PD-L1 agent. Here, EHMT2 is linked to bladder transitional cell carcinoma.