Figure 3.

Pharmacological inhibition or genetic ablation of RON cooperates with aCTLA4, but not with aPD1, to control breast cancer progression in mice. A. Growth curves of orthotopically transplanted PyMT-NP tumors in wild type (WT) mice following treatment with vehicle control (black; n = 30); RONi alone (green; n = 17); aCTLA-4 alone (blue; n = 13); or RONi+aCTLA-4 (red; n = 13). Each line represents tumor growth in an individual mouse. The vehicle-treated group is overlaid on each graph for comparison purposes. All treatment was initiated when the tumors reached 100 mm³ in size (day 0). The dashed line indicates the partial response cutoff of 300% increase in tumor size (two tumor doublings). Color-coded arrows indicate average percent change in tumor size at the endpoint (day 24) B. Percent of mice in each treatment group categorized as refractory to treatment or showing partial or complete response. Statistical analysis was performed via Fisher’s exact test, comparing the numbers of refractory tumors and tumors with clinical benefit (complete response and partial response combined). Tumor growth curves for aPD-1 experiments are shown in Fig S7b (aPD-1; n = 14) (RONi+aPD-1; n = 16) C. Change in tumor growth rates with treatment, compared between groups using one-way ANOVA and Tukey’s correction. Log-transformed growth curves for each mouse are shown in Fig S7a,c. D. Growth curves of orthotopically transplanted PyMT-NP tumors in RON TK-/- hosts: WT vehicle (black; n = 4); RON TK-/- vehicle (green; n = 12); RON TK-/- aCTLA-4 (blue; n = 13); RON TK-/- RONi+aCTLA-4 (red; n = 12). Mice were treated as in panel A. E. Percent of mice in each RON TK-/- treatment group categorized as in panel B. F. Change in the growth rate of tumors following treatment in RON TK-/- hosts. Log-transformed growth curves for each mouse are shown in Fig S7d. (ns) p > 0.05, (*) p ≤ 0.05, (**) p ≤ 0.01, (***) p ≤ 0.001, (****) p ≤ 0.0001.