MALT1/MTORC1 inhibition suppresses growth of ABC-DLBCL through decreased proliferation and increased cell death. Apoptosis for rapamycin (Rapa) combinations with structurally unrelated MALT1 inhibitors MI-2 (A) and C3 (B) was studied using annexin V/DAPI staining in the indicated cell lines. Cells were treated for 4 days, and the following drug concentrations were used: 1 nM Rapa, 250 nM MI-2 (100 nM for HBL-1), and 1 μM C3. Results are percentage of cells ± standard error of the mean (SEM) of ≥2 independent experiments in triplicate. CFSE dilution assay results for rapamycin combinations with MI-2 (C) or C3 (D) in the indicated cell lines, treated as above. The y-axis shows CFSE mean fluorescence intensity fold to vehicle ± SEM of ≥2 independent experiments in triplicate. (E) OCI-Ly3 cells were seeded in 2-dimensional (2D) or 3D conditions, and their response to C3, rapamycin, or their combination was evaluated using Calcein-AM (for live cells) and propidium iodide staining (for dead cells). (F) Plot for live/dead quantification of OCI-Ly3 cells grown in 2D vs 3D conditions for 6 days. Results are percentage of cells ± SEM of 4 replicates. *P < .05, **P < .01, ***P < .001, 1-way analysis of variance corrected for multiple comparisons 5% FDR. ns, not significant (P > .05).