Clinical studies combining SAHA with ICIs are ongoing (NCT02638090, NCT02538510, NCT02619253, NCT02395627), the most crucial SAHA-controlled mechanisms and biomarkers to discriminate priority patients who will and will not respond remained to be defined.46 47 Preclinical studies suggest that the mechanisms might be attributed to the expression of immune-related genes and tumor antigens.48 This study uncovered that SAHA increased the acetylation and proteasome degradation of SOX2, thus relieving the SOX2-related inhibitory function on T-cell antimelanoma immunity. The gene discussed is SOX2; the disease is neoplasm.