Fig. 7

Inhibition of CARD11-BCL10-MALT1 (CBM) signaling enhances anti-tumor immunity. a Schematic representation of the B16F1 tumor model combined with the acute deletion of Bcl10 in regulatory T cells (Tregs): on day 1, 1 × 10⁵ B16F1 tumor cells were subcutaneously injected into the flanks of Bcl10^+/+;Foxp3^eGFP-CreERT2 and Bcl10^fl/fl;Foxp3^eGFP-CreERT2 mice. Tamoxifen was administered every other day deleting the Bcl10^fl/fl alleles in newly emerging Tregs until the final analysis on day 28. b Quantification of the tumor size in Bcl10^+/+;Foxp3^eGFP-CreERT2 and Bcl10^fl/fl;Foxp3^eGFP-CreERT2 mice on day 28 after tamoxifen treatment. Representative tumors of Bcl10^+/+;Foxp3^eGFP-CreERT2 (left) and Bcl10^fl/fl;Foxp3^eGFP-CreERT2 (right) male mice are depicted on the right side of the graph. Scale bar represents 1 cm. Tumor size was calculated as follows: V = (L × W²) × 2⁻¹, where L is the length of tumor (mm) and W the width of tumor (mm). Statistical significance between genotypes was assessed by a two-tailed Mann–Whitney U test. c Schematic representation of the B16-OVA tumor model in wild-type mice combined with a pharmacological inhibition of the MALT1 protease activity: B16-OVA cells were subcutaneously injected into the flanks of C57Bl/6  mice, followed by a vaccination with OVA + CpG on day 8. On days 11 and 13, mice were treated with either the MALT1 inhibitor mepazine or vehicle (phosphate-buffered saline (PBS)/5% dimethyl sulfoxide (DMSO)) and analyzed on day 15. d, e Quantification of the ratio of tumor-infiltrating d CD8⁺IFN-γ⁺ cells to the frequency of CD8⁺ cells and e CD4⁺Foxp3⁻IFN-γ⁺ cells to the total percentage of CD4⁺Foxp3⁻ T cells after re-stimulation of enriched tumor-infiltrating lymphocytes with phorbol myristate acetate (PMA) (100 nM)/ionomycin (1 µM). Statistical significance was calculated with a two-tailed unpaired Student’s t test. f Tumor size on day 15 following treatment on days 11 and 13 with either vehicle or mepazine (16 mg kg⁻¹ bodyweight). Statistical significance between groups was assessed with a one-tailed Mann–Whitney U test. g Quantification of the ratio of tumor-infiltrating Tregs to the total percentage of T cells. A statistical difference of the mean was calculated by a two-tailed unpaired Student’s t test; (ns) not significant. Bars in b, d–g indicate the mean ± SD. IFN-γ interferon-γ. Source data are provided as a Source Data File