Mi-2β silencing induces the immune response to anti-PD-1 antibody treatment in “cold” melanoma, and the effects are mediated by interferon-stimulated genes (ISGs), such as Cxcl9 and Cxcl10. Mechanistic studies demonstrate that Mi-2β controls the chromatin accessibility of ISGs by binding to EZH2 and promoting its methylation. This evidence concerns the gene CHD4 and melanoma.