Fig. 7: Gene signatures correlate with treatment efficacy and reveal drug mechanism of action.

a Gene signatures for each individual treatment regimen manually composed on the basis of differentially expressed genes between control and indicated treatment group of the MEKi/CD40 Ab experiment, as performed on four mice per treatment group of the experiments shown in Fig. 3a–c. In GEM/CD40 Ab PDA30364 experiments, 120 mg kg⁻¹ GEM was administered on treatment days 1, 5, and 12 and anti-CD40 Ab on days 3, 4, 6, and 14; mean ± s.e.m. Each treatment group consisted of at least seven animals. Four mice per treatment group were analyzed on day 22/23 after tumor inoculation. b Tumor growth of GEM/CD40 Ab or monotherapy groups. Mean±s.e.m. Two-way ANOVA with post hoc Fisher’s LSD test (treatment groups vs. control; day 25). c Waterfall plots of GEM/CD40 Ab and MEKi/anti-CD40 Ab on day 22 after tumor inoculation. Each bar represents one individual mouse. Some data as in Fig. 3c and 7b. d Treatment of PDA30364 tumor-bearing mice with 120 mg kg⁻¹ GEM or nanoparticle albumin bound paclitaxel (nAbP). nAbP was administered on treatment day 1 and GEM was dosed on days 1, 5, and 12. Anti-CD40 Ab on days 3, 4, 6, and 14. Mean ± s.e.m. Four mice per treatment group were sacrificed on days 22/23 after tumor inoculation. Note, the control, anti-CD40 Ab, GEM, GEM/anti-CD40 Ab groups are the same as in b. Two-way ANOVA with post hoc Fisher’s LSD test (treatment groups vs. control; day 25). Significance levels are indicated by asterisks (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001).