Dual Targeting with EZH2 Inhibitor and STING Agonist to Treat Melanoma.

The immunotherapy era has ushered in enormous promise for cancer, largely led by progress in melanoma management. However a significant fraction of melanoma patients suffers early progression or relapse due to treatment resistance. Immunologically cold tumors are often refractory to immunotherapies and are associated with a lack of interferon signalling and antigen presentation. In their new article, Xu et al. (2022) demonstrate that the epigenetic modifier enhancer of zeste homolog 2 (EZH2) regulates expression of the innate immune signalling factor STING and that dual targeting of EZH2 and STING induces interferon signalling, major histocompatibility complex expression and synergistically reduces tumor growth in a preclinical model. Strategies such as this stand to improve therapeutic opportunities for otherwise refractory tumor contexts.