Fig. 2

Domatinostat increases gene expression signatures correlated with the clinical benefit of PD-1 blockade. CT26 tumor model (n = 10 per group) as in Fig. 1; end-of-treatment tumors were analyzed for gene expression by RNA-seq. a, Heatmap of antigen-processing machinery (APM) and major histocompatibility complex (MHC) class I and II gene expression with scores per sample. b, APM/MHC signature score based on (a). c, Ifng gene expression. d, IFN-γ response signature score (MSigDB hallmark gene set). e, Gene set enrichment analysis (GSEA) plot for the correlation of domatinostat-regulated gene expression with the IFN-γ response signature (MSigDB). NES: normalized enrichment score; FDR: false discovery rate. f, Heatmap of pembrolizumab response signature gene expression (adapted from Ayer’s T cell inflamed signature) [5]. g, Pembrolizumab response (RE) signature score based on (f). h, Nivolumab response (RE) signature score [27]. b, c, d, g, h, Mean ± SD showing all data points; signature scores were calculated by mean log2(TPM + 0.001) of their respective member genes; P-values: Mann-Whitney test, two-tailed. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant. TPM, transcripts per million; DGE, differential gene expression