KMT2D and cancer: Given the frequent loss of function mutations and epigenetic silencing of MLL3 and MLL4 in diverse cancer types33,73, our findings suggest that the genetic and expression status of MLL3 and MLL4 may serve as biomarkers for cancer patient stratification in immune checkpoint blockade therapies such as anti-PD-1 or anti-PD-L1 treatment and in predicting immunotherapeutic efficacy and clinical prognosis.