Fig. 7
TAMs support CI-deficient tumors growth and their inhibition enhances metformin effects. a Representative dot plots displaying macrophage populations expressing CD206, Arg1, and iNOS in HCT+/+ and HCT−/− xenografts, and in fluorescence minus one (FMO) controls. iNOS (light blue) was set as the first front and Arg1 (dark blue) as the second front population, compared to CD206 (dark purple) and remaining immune cells (green). b Flow cytometry analysis of macrophage subpopulations markers CD206, Arg1, and iNOS in 143B and HCT tumors at day 30 post injection in ICRF nude mice. Statistics for 143B: n = 4, df = 6, t(CD206) = 3.756, t(Arg1) = 3.219, t(iNOS) = 3.143. Statistics for HCT: n = 3, df = 4, t(CD206) = 14.96, t(Arg1) = 3.348. Data are mean + s.e.m. c Tumor growth curves of HCT−/− xenografts in ICRF nude mice treated with or without clodronate [n = 8, df = 14, t(day 47) = 3.524]. Representative tumors are shown. Scale bars: 1 cm. Data are mean ± s.e.m. d Hematoxylin/eosin (HE) staining of HCT−/− xenografts in ICRF nude mice treated with or without clodronate. Scale bars: 50 µm. e Tumor growth curves and volume at day 27 post-treatment of HCT−/− xenografts in CD-1 nude mice, treated with metformin (2 mg mL−1 in drinking water) or PLX-3397 (1.5 mg per day by oral gavage) alone and in combination [data were log-transformed, n = 5–7, df(metformin versus double treatment) = 10, t(metformin versus double treatment) = 2.539]. Data are mean ± s.e.m. In each panel, statistical significance is specified with asterisks (*p < 0.05, **p < 0.01, ***p = 0.001)
