Figure 6.

Entinostat induces an adrenergic-to-mesenchymal cell lineage shift which is accompanied by increased immunogenicity. (A) Cell lineage score of untreated (blue) and entinostat-treated (red) 691b organoids. Adrenergic (A) and mesenchymal (M) scores were calculated for each sample based on the gene signatures outlined by van Groningen and colleagues.7 (B) Expression of representative adrenergic (purple) and mesenchymal (green) signature genes in untreated and entinostat-treated 691b organoids. Log2 gene expression values were z-score transformed for heatmap visualization. (C) Correlation plot between mesenchymal minus adrenergic score (M−A score) and IA score in untreated (blue) and entinostat-treated 691b organoids (red). X-axis denotes organoids ranked in increasing order of (M–A) score. Cells were treated for 48 hours with 2.5 µM entinostat or vehicle control. Both groups: n=5. IA, immune activation; M−A, mesenchymal minus adrenergic.