Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator and in prostate cancer, it was found that EZH2 negatively regulates the expression of interferon stimulated genes (ISGs) such as programmed cell death protein 1 (PD-1) and major histocompatibility complex, creating an immunosuppressive tumor microenvironment and increasing resistance to immune checkpoint blockade (ICB) therapies (16). The gene discussed is EZH2; the disease is prostate cancer.