Fig. 5: OTX-2002 improves efficacy of Anti-PD1 / PD-L1 therapy. | Nature Communications

Fig. 5: OTX-2002 improves efficacy of Anti-PD1 / PD-L1 therapy.

From: Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models

Fig. 5

A MFI calculation (gating strategy Fig S7A, B) using fluorophore conjugated anti-PD-L1 antibody in treated Hep 3B (left) or SK-HEP-1 (right) cells. Results are from one independent experiment (Hep 3B, n = 2 technical replicates for untreated and NC mRNA, n = 3 technical replicates for all other groups; SK-HEP-1, n = 3 technical replicates for untreated and NC mRNA, n = 4 technical replicates for all other groups) and were repeated once. B Evaluation of Myc mRNA (left) and Myc promoter methylation (right) using murine muMyc-EC in the Hepa1.6 cell line. Results are from one independent experiment (Myc mRNA expression, n = 3 technical replicates for all treatments; Myc promoter methylation at 24 h, n = 9 technical replicates for all groups, at 48 h, n = 5 technical replicates for muMyc-EC, n = 8 technical replicates for NC mRNA) and were repeated once. C In vivo evaluation of single agents and combinations in Hepa1.6 tumors grown in normal mice. Significance measured using two-way ANOVA comparing muMyc-EC, Anti-PD-1, or Anti-PD-L1 single agents to combinations with adjusted p-values for multiple comparisons; ***P = 0.0002 and ****P < 0.0001. Results are from one independent experiment (n = 12 mice for PBS group, n = 10 mice for all other groups) and were repeated once. D Survival curves for combination study in (C) with mice removed at >2000 mm3. Significance was measured using Log-rank (Mantel-Cox) test comparing muMyc-EC, Anti-PD-1, or Anti-PD-L1 single agents to combinations (****P < 0.0001). E Hepa1.6 treated tumors collected on Day 16 for TIL analysis. Results (E, F) are from one independent experiment (n = 14 mice per group) and were repeated once. F Measurement of TILs using flow cytometry (gating strategy Fig. S8). Percentage of immune cells (left) or regulatory T-cells (right) in treated tumors. Results are from one independent experiment (n = 6 tumors for PBS, n = 6 tumors for muMyc-EC, n = 4 tumors for Anti-PD-1, n = 5 tumors for muMyc-EC+Anti-PD-1) and were repeated once. Significance measured using one-way ANOVA with adjusted p-values; PBS vs. muMyc-EC *P = 0.0348, PBS vs. Anti-PD-1 **P = 0.0035, and Anti-PD1 vs. muMyc-EC + Anti-PD1 **P = 0.0042. For all relevant panels error bars represent mean (±) standard error of the mean (SEM). Source data are provided as a Source Data file.

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