Fig. 5: Treatment with Mitochondrial Complex I inhibitor, metformin, prolongs survival of the AITL mouse model. | Cell Death Discovery

Fig. 5: Treatment with Mitochondrial Complex I inhibitor, metformin, prolongs survival of the AITL mouse model.

From: Dependence on mitochondrial respiration of malignant T cells reveals a new therapeutic target for angioimmunoblastic T-cell lymphoma

Fig. 5

A Splenic lymphoma cells from plck-GAPDH mice were injected intravenously into recipient NSG mice (n = 13), which were treated with vehicle (n = 7) or the complex I inhibitor metformin (n = 6) added to the drinking water. Survival curves for mice are shown in B. Mice were sacrificed at endpoint or 155 days post-transplant (*p < 0.05, Mantel–Cox test). C FACS analysis of percentage of CD4+ PD-1high cells per total CD4+ T cells in the spleen of the indicated treatment groups at sacrifice (mean ± SD, Vehicle (Veh): n = 6; Metformin (Met): n = 6); **p < 0.01). D Total number of CD4+ PD-1high cells in the spleen of vehicle or metformin-treated groups; (mean ± SD, Veh: n = 6; Met: n = 6); ****p < 0.0001). E FACS analysis of percentage of GC B cells (GL-7+ CD95+) on total B cells (gated on CD19 + B220+ cells) in the spleen of the indicated treatment groups at sacrifice (mean ± SD, Veh n = 6; Met n = 6; *p < 0.05). F Total number of GC B cells (GL-7+ CD95+) in the spleen of vehicle or metformin-treated groups, (mean ± SD, Veh: n = 6; Met: n = 6; ****p < 0.0001). G FACS analysis of CD4+ T cells stained for mitochondrial content by Mitotracker green (MTG) in the spleen of the indicated treatment groups at sacrifice (mean ± SD, veh n = 7; Met n = 4; *p < 0.05). H Analysis of the metabolic dependance on glucose or mitochondria for the CD4+ T cells in the spleen of the indicated treatment groups at sacrifice by SCENITH metabolic analysis (mean ± SD, veh n = 6, Met n = 5; **p < 0.01, *p < 0.05). I Percentage of CD8+ T cells per total CD3+ cells in the spleen of the indicated treatment groups at sacrifice (mean ± SD; ***p < 0.001, veh n = 7; Met n = 5). J Splenocytes isolated from metformin or control-treated mAITL engrafted NSG mice were activated for 6 h with PMA/ionomycin in the presence of golgi-stop, then surface stained for CD8 followed by intracellular staining for INFγ, perforin, and granzyme B and analyzed by FACS (mean ± SD, n = 4; ***p < 0.001, ****p < 0.0001). K Analysis of the metabolic dependance on glucose or mitochondria for the CD8+ T cells in the spleen of the indicated treatment groups at sacrifice by SCENITH metabolic analysis. (mean ± SD, vehicle n = 3, Metformin n = 3; *p < 0.01, ****p < 0.0001).

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