Figure 6 from Trabectedin Enhances the Antitumor Effects of IL-12 in Triple-Negative Breast Cancer

CD8a depletion abrogates IL-12/trabectedin-induced tumor control. BALB/c mice were inoculated with 4T1 cells. Once tumors reached ∼50 mm³, mice were either depleted of CD8a⁺ cells using α-CD8a antibody (n = 7) or treated with an IgG isotype control antibody (n = 6). CD8a⁺ depletion was performed through intraperitoneal injection of an αCD8 antibody 1 day prior to the start of IL-12 and trabectedin treatment (at a dose of 200 μg) and every 4 days thereafter (at a dose of 100 μg). Nondepleted mice were treated with the same dose of control antibody at the same time points. Both groups were treated with 0.5 μg IL-12 i.p. 3 ×/week and 0.15 mg/kg trabectedin i.v. 1×/week. A, Tumor growth curves throughout the 8-day treatment. B, Tumor images after excision. C, Individual tumor growth curves for IL-12 and trabectedin + IgG–treated mice and IL-12 and trabectedin + αCD8–treated mice. D, Plasma cytokine and chemokine levels in mice (n = 4–6) at day 16. For statistical analyses of tumor volumes, linear mixed modeling was used to model longitudinal tumor volume for mice under each treatment. Comparisons were done at each time point and averaged across all time points using t-statistics. The Tukey–Kramer method was used for adjusting raw P values for multiple comparisons across treatment groups. Statistical analyses of bar graphs were performed using two-tailed unpaired student t tests. Data represent mean ± SEM. *, P < 0.05; **, P < 0.01. Trab, trabectedin.