Fig. 5: Glutamine metabolism epigenetically silences BATF2 and remodels oxidative phosphorylation to dampen the STING-IFN-I response.

a, b BMDM were cultured in media containing glutamine (0 g/L, 0.5 g/L or 5.0 g/L) for 24 h, followed by transfection with STING agonists. c, d BMDM were cultured in media containing 0.5 g/L (c) or 5 g/L (d) glutamine and transfected with cGAMP with or without of BPTES. Data are compared using one-way ANOVA. e, f Ifn-β in the supernatant from this figure (a, b) was quantified by ELISA. g BMDM were cultured in media containing varied levels of glutamine and then transfected with cGAMP. The protein lysates were subjected to immunoblotting. Data represent two biologically independent experiments. h BMDM were cultured in media containing varied levels of glutamine and transfected with ISD. ChIP analysis of the H3K27me3 mark in the promoter regions of Batf2 is compared using one-way ANOVA. i BMDM were cultured in media containing 0 g/L or 5.0 g/L glutamine for 24 h and transfected with ISD and OCR was compared. j Wild-type and Batf2^−/− BMDM were transfected with ISD and OCR was compared. k Female C57BL6/J mice on a control diet or glutamine-rich diet were implanted with NOOC1 cells subcutaneously. Mice were treated with PBS or c-di-AMP intratumoural injection (n = 8). l, m The combination of CDA and JHU-083 was administered for 2 weeks (n = 8). n UMAP rendering of scRNA-Seq of the TILs separated from 5k (n = 8 mice per group), shown above is generated. o The relative cluster size change percent is shown. p The Batf2 expression level in each cluster is shown. q The expression levels of Batf2 were compared using a Wilcoxon test. r Bulk RNA-Seq was performed for 15 HNSCC specimens. A correlation analysis between BATF2-IFN-I target genes and glutamine metabolism is shown. Data in this figure (a–h) represent biologically independent experiments (n = 3, mean ± SEM). Data in this figure (i, j) were compared by an unpaired two-tailed t-test and represent biologically independent samples (n = 3, mean ± SEM). Comparisons in (a, b and e, f) were made using two-way ANOVA, followed by multi-comparison tests. The tumour growth in this figure (k–m) was compared using the generalized estimating equation (GEE) model.