Extended Data Fig. 3: T cell signal attenuates the therapeutic response to MALT1 inhibition in human and canine ABC-DLBCLs.
a, Survival (normalized to vehicle-treated) of human ABC-DLBCL PDXs cultured in organoids with and without CD40L after 48-h culture, followed by 48-h treatment with 500 or 2000 nM MI2 treatment or 1000 nM MLT-748 MALT1 inhibitor compound. One-way ANOVA with Tukey’s multiple-comparison test (mean ± s.e.m., n = 4, PDX#4; n = 5, PDX#5, where each dot is a hydrogel-based organoid). b-c, Survival (normalized to vehicle-treated) human ABC-DLBCL PDX cells cultured in organoids with and without CD40L after 48-h culture, followed by 48-h treatment with MALT1 inhibitor MI2 at 500 nM (b) and 2000 nM (c) treatment. One-way ANOVA with Tukey’s multiple-comparison test (b) and two-tailed unpaired t-test (c), (mean ± s.e.m., n = 3 for (b), n = 5 for (c), where each dot is a hydrogel-based organoid). d, Survival (normalized to vehicle-treated) of HBL1 cells cultured in organoids with baseline stromal cell and CD40L-transduced stromal cell after 48-h culture, followed by 48-h treatment with 500 nM MI2 treatment. Two-tailed unpaired t-test (mean ± s.e.m., n = 7). e, Survival (normalized to vehicle-treated) of canine PDX cells cultured in organoids with and without CD40L-stromal cells after 48-h culture, followed by 48-h treatment with 2000 nM MI2 treatment. Two-tailed unpaired t-test (mean ± s.e.m., n = 5 for -CD40L and n = 6 for +CD40L).
