Fig. 7: Itaconate and metformin can regulate MSDC metabolic fitness in vivo and determine lymphoma treatment outcome. | Nature Communications

Fig. 7: Itaconate and metformin can regulate MSDC metabolic fitness in vivo and determine lymphoma treatment outcome.

From: Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies

Fig. 7: Itaconate and metformin can regulate MSDC metabolic fitness in vivo and determine lymphoma treatment outcome.The alternative text for this image may have been generated using AI.

Survival of EL4 tumors bearing mice treated with 4OI (50 mg/kg) or vehicle every 3 days; Set (A) received isotype antibody and set (B) received anti-Gr1 (twice weekly; i.p.; 1 mg/kg). Each set received propranolol (daily; i.p.; 1 mg/kg), or doxorubicin (day 7; i.v.; 4 mg/kg), or both (**p = 0.0019; **p = 0.0027). Two-sided Mantel-Cox log rank test. C Survival of β2-AR-/- and WT mice bearing EL4 treated with 4OI (50 mg/kg) or vehicle every 3 days, then doxorubicin (day 7; i.v.; 4 mg/kg). Two-sided Mantel-Cox log rank test. D−G WT mice were pre-treated with 4OI (50 mg/kg) or vehicle for 4 h, then doxorubicin (i.v.; 20 mg/kg). After 18 h, the apoptosis rate was measured in (D) CD11b+Ly6C+Ly6G- (M-MDSC) and (E) CD11b+Ly6C+Ly6G+ (PMN-MDSC). Mitochondrial ROS (mROS) was detected on (F) M-MDSCs, and (G) PMN-MDSCs (*p < 0.05; **p < 0.01; ***p < 0.001). One-way ANOVA with Bonferroni’s multiple comparison tests. Data are presented as mean ± SEM. n = 4 mice per group. Nrf2 expression in (H, I) M-MDSCs and (J, K) PMN-MDSCs isolated from mice treated as in (D−G) (*p < 0.05; **p < 0.01; ****p < 0.0001). One-way ANOVA with Bonferroni’s multiple comparison tests. Data are presented as mean ± SEM. n = 4 mice per group. L Survival of EL4 bearing Aconitate Decarboxylase 1 deficient (Acod1-/-) compared to WT mice treated with doxorubicin (day 7; i.v.; 4 mg/kg) (**p = 0.0031). Two-sided Mantel-Cox log rank test. M Survival of EL4 bearing mice receiving metformin (250 mg/kg; drinking water) or doxorubicin (day 7; i.v.; 4 mg/kg), or both. Set (M) received isotype control and set (N) received anti-Gr1 (twice weekly; i.p.; 1 mg/kg) (*p = 0.0180). Two-sided Mantel-Cox log rank test. WT mice pre-treated with metformin (250 mg/kg; drinking water; 7 days) received doxorubicin (i.v.; 20 mg/kg). After 18 h, the apoptosis rate was measured in by (N, O) Annexin V assay (*p = 0.0157; **p = 0.0024; ****p < 0.0001) and (P, Q) CaspGLOW™ Caspase-3 staining assay (*p = 0.0331; **p = 0.0055; ***p = 0.0005). One-way ANOVA with Bonferroni’s multiple comparison tests. Data are presented as mean ± SEM. n = 4 mice per group. Source data containing independent experiments raw data are provided as a Source Data file.

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