MTORC1-MALT1i combination promoted ABC-DLBCL regression in vivo. (A) Experimental scheme of the in vivo MI-2/rapamycin combination experiment. (B) Tumor growth curve for TMD8 xenografts (n = 5 per group). Mice were treated with vehicle, 25 mg/kg per day of MI-2, 1 mg/kg per day of rapamycin, or their combination for 15 days. (C) Change in tumor volume at day 15 compared with day 0 for each mouse. The p values were determined using analysis of variance and Tukey's multiple-comparisons test. (D) Survival curves for mice in (B). The P values were calculated using log-rank Bonferroni-Hochberg-adjusted survival analysis. (E) Median survival for the different treatment groups in (D). (F) Dosing schedule for a short-term experiment to evaluate the effect of the combinations in signaling. Arrows, dosing event. (G) Immunohistochemistry was used to study p-S6-S235/6 levels in TMD8 xenografted mice that were treated twice (28 hours) with the indicated inhibitors and their combinations, as indicated in (F). Samples were stained with anti-phospho-S6 antibody. (H) p-S6-S235/6 levels in TMD8 xenografted tumors treated with the indicated drugs and combinations. Data correspond to 5 high-powered fields per tumor in 3 or 4 mice per treatment group. *P < .05, **P < .01, ****P < .0001. ns, not significant (P > .05).