Extended Data Fig. 1: Different metabolic states of T_reg cells in tumours and inflammatory contexts.

a, Biochemical pathways for de novo lipid synthesis. b, Enrichment plots for SREBP gene targets in intratumoral versus PLN T_reg cells from Foxp3^Cre mice bearing B16 melanoma (n = 4 per group). c, Top 15 upstream transcriptional regulators enriched in intratumoral T_reg cells as compared with PLN T_reg cells from Foxp3^Cre mice bearing B16 melanoma (n = 4 per group), analysed by Ingenuity pathway analysis. d, e, Enrichment of SREBP gene targets in intratumoral and PLN T_reg cells from public scRNAseq datasets for mouse B16 melanoma^7,8. f, g, Enrichment of SREBP gene targets in intratumoral T_reg cells from individuals with breast cancer⁹ (f) or HNSCC¹⁰ (g). h, Enrichment plots for SREBP gene targets from the public dataset¹¹ of in vivo activated T_reg (aT_reg) compared with resting T_reg (rT_reg) cells in the acute inflammation model. i, j, T_reg cells were isolated from spleen and CNS of MOG-induced Foxp3^RFP EAE mice for scRNAseq analysis. i, Unsupervised clustering of cells in the spleen and CNS was analysed by UMAP: left, splenic and CNS cells are annotated with different colours; right, the expression of SREBP gene targets is visualized. j, Comparison of SREBP gene targets between splenic and CNS T_reg cells on the violin plot. k, Relative (values in splenic samples were set to 1) uptake of a fluorescent glucose analogue, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), in splenic and intratumoral T_reg cells from mice bearing MC38 tumours on day 21 after tumour inoculation (n = 17). l, Relative (values in splenic samples were set to 1) uptake of 2-NBDG (n = 14) in T_reg cells from the spleen and spinal cord of MOG-induced EAE mice on day 16 after MOG immunization. m, Expression of Scap mRNA was examined in T_reg, naive CD4⁺ and CD8⁺ T cells from Foxp3^CreScap^+/fl and Foxp3^CreScap^fl/fl mice under steady state (n = 5 samples per genotype). n, Heat map showing expression of SREBP gene targets, normalized by row (z-score), in tumour-infiltrating T_reg cells from mice bearing B16 melanoma on day 19 after tumour inoculation (n = 4, Foxp3^CreScap^+/+ or Foxp3^CreScap^+/fl control mice; n = 3, Foxp3^CreScap^fl/fl mice). o, Foxp3^{GFP–Cre–ERT2}Scap^+/flRosa26^YFP and Foxp3^{GFP–Cre–ERT2}Scap^fl/flRosa26^YFP mice were injected with MC38 cells without tamoxifen treatment (n = 6 mice per genotype). Tumour growth was measured. ***P < 0.001; NS, not significant; two-tailed unpaired Student’s t-test (k–m) or two-way ANOVA (o). Data are means ± s.e.m. in d–g, j–m, o. Data are representative of two (o) or compiled from two (k, l) independent experiments.

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