Fig. 7. EZH2 inhibition increases the efficacy of paclitaxel chemotherapy in a syngeneic murine TNBC model.

a Immunoblots show H3K27me3 and MHC-I protein expression at 1, 3, 5, 7 days after a single 10 μM treatment with tazemetostat, CPI-1205, or MAK-683. b Histograms show the distribution and c quantification of cell-surface MHC-I protein expression 5 days after a 10 μM treatment with the indicated PRC2 inhibitors. Results are representative of three experiments. Error bars represent the standard error of the mean. d Treatment schedule for mice bearing syngeneic 4T1 xenograft tumors. Mice were treated with vehicle, twice daily (BID) with 250 mg/kg tazemetostat, twice a week with 10 mg/kg paclitaxel, or the combination of tazemetostat and paclitaxel. Results are representative of ten tumors. e Graphs show 4T1 tumor volume (mm³) across time of mice treated with vehicle, tazemetostat, paclitaxel, or the combination. Error bars represent the standard error of the mean. Significance determined by two-tailed Student’s t-tests, *p = 0.0353. f Barplot shows the distribution of final tumor weight (mg) from mice treated with vehicle, tazemetostat (TAZ), paclitaxel (TAX), or the combination (TAZ + TAX). Significance determined using Dunnett’s multiple comparison test. *p = 0.0423. g Plot shows IHC quantification of intratumor CD3+ T-cells in 4T1 xenograft tumors by treatment group. h Schematic shows CpG methylation and H3K27me3 epigenetic states in non-mesenchymal TNBC or mesenchymal TNBC with or without EZH2 inhibition.