FIGURE 4 from EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas

ChIP-seq of human patient-derived organoids confirms direct regulation of MHC and pro-T cell cytokines by EZH2. A, Peaks called at FDR 1E-7 for ChIP-seq using the chromatin marks H3K27me3, H3K27ac, and H3K4me3 in PDTs from the indicated treatment groups. Wiggle plots for H3K27me3, H3K27ac, and H3K4me3 histone mark enrichments, and matched RNA-seq tracks in PDTs from the indicated treatment groups for the genes: HLA-DRA (B), CXCL9/10/11 (C), ALOX15 (D), IL1B (E), H3K27me3 (F) peaks were called for each treatment group and GREAT was used to identify associated genes, which were then depicted by Venn diagram. G, H3K27me3 peaks that were gained or increased more than 2-fold with IFNγ treatment, and lost with EPZ6438 treatment were linked to associated genes by GREAT. The Venn diagram shows the overlap of these genes with those significantly upregulated in combination treated versus IFNγ-treated tumoroids. See also Supplementary Fig. S4.