Fig. 3

High Histidine Metabolism Suppresses the Antitumor Function of T Cells. (A) t-SNE plot displaying T cells clustered into 12 distinct cell clusters via dimensional reduction. (B) Annotation based on marker gene expression classified T cells into five subpopulations: Tem-GZMA + cells, Tn-CCR7 + cells, HSP-T-HSP + cells, Treg-Ctla4 + cells, and Trm-CD69 + cells. (C) t-SNE plot dividing T cells into two groups based on histidine metabolism levels: high histidine metabolism group(left) and low histidine metabolism group(right). (D) Proportions of T cell subpopulations within the high and low histidine metabolism level groups. (E) Heatmap showing intercellular communication intensities mediated by various signaling axes among different T-cell subpopulations. (F) Heatmap illustrating CLEC, MIF, SPP1, PARs, MHC-II, and VTN signaling intensities in the high and low histidine metabolism groups. (G) Bubble chart of GSEA outcomes for T-cell subpopulations in high vs. low histidine metabolism conditions. (H) Bubble chart of GO enrichment analysis showing how histidine metabolism affects T-cell function. (I) Representative flow cytometry gating strategies for mouse splenic lymphocytes and their differentiation, activation, and exhaustion status under different histidine concentrations. (K) The bar chart displays the differentiation, activation, and exhaustion of CD4 + T cells (upper) and CD8 + T cells (lower) after co-culture with different concentrations of histidine treatment. Error bars represent the SD from five independent experiments, *P < 0.05, **P < 0.01, ***P < 0.001