Fig. 5: Knockout of MAT2A reduces SAM production and suppressive in vivo tumorigenesis and T-cell dysfunction in HCC.
From: Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma
a Representative immunoblot of Hep-55.1 cells with stable MAT2A-KO and control of three independent experiments. Corresponding molecular weight markers of each blot were labeled at the right edge of image and the original full scan images could be find in the Source Data. b Intracellular concentration of SAM of Hep-55.1 cells with stable MAT2A-KO and control. Bar, mean; error bar, S.D. n = 3. Statistical significance is determined by two-sided independent t test. c Representative livers of mice carrying Hep-55.1 tumors with and without MAT2A-KO (left). The average ratio of tumor-to-liver weight is shown at the left panel (n = 9 in Cas9-Ctrl and n = 10 in MAT2A-KO). Bar, mean; error bar, S.D. Statistical significance is determined by two-sided independent t test. d Representative expressions of TIM3, LAG3, TIGIT, and PD1 on CD8+ T cells isolated from tumor-carrying livers and spleens. The average fraction of cells positive for each markers from liver or spleen were shown at the right two panels (n = 9 in Cas9-Ctrl, n = 10 in MAT2A-KO). Bar, mean; error bar, S.D. Statistical significance is determined by two-sided independent t test. e Representative expressions of interferon-gamma (INFγ) and tumor necrosis factor- alpha (TNFα) of CD8+ T cells after PMA/ionomycin stimulation. The average fraction of CD8+ T cells positive for INFγ and TNFα is summarized by bar plots. Lymphocytes obtained from tumors (n = 4 biological independent samples from Cas9-Ctrl and from MAT2A-KO tumors), liver (n = 7 biological independent samples from Cas9-Ctrl mice, n = 8 in biological independent samples MAT2A-KO) and spleen (n = 7 biological independent samples in Cas9-Ctrl, n = 8 biological independent samples in MAT2A-KO) were stimulated with PMA/ionomycin for 4 h and stained for cytokine expressions. Bar, mean; error bar, S.D. Statistical significance is determined by two-sided independent t test. Source data are provided as a Source Data file.
