MSI-H tumors hijack TREX1 to suppress intrinsic cGAS–STING-mediated CD8 ⁺ T cell activation. (A) UMAP plot showing the distribution of different CD8⁺ T cell subtypes in MC38, MC38-Trex1^−/−, MC38-Cgas^−/−, and MC38-Trex1^−/−Cgas^−/− samples. (B) Expression of highly expressed IFN response and immune cell activation-related genes in CD8⁺ T cell T_2 across different CD8⁺ T cell subtypes. (C) Velocities derived from the dynamical model for CD8⁺ T cell are projected into a UMAP-based embedding. (D) UMAP plot showing gene expression of Cd83, Ifitm2, and H2-Aa, with the red circle indicating location of CD8_T_2 cells. (E) GSEA analysis showing activated and suppressed hallmark pathways in CD8_T_2 vs. CD8_T_5 cells; the point color indicates the adjusted P value, and the point size indicates the upregulated gene count in each signal pathway. (F) Dot plot shows the significantly enriched hallmark pathways for highly expressed genes in CD8_T_2 vs. CD8_T_5 cells; the point color indicates the adjusted P value, and the point size indicates the upregulated gene count in each signal pathway. (G) C57BL/6 mice (n = 10) were transplanted s.c. with 1 × 10⁷ MC38, MC38-Trex1^−/−, MC38-Cgas^−/−, and MC38-Trex1^−/−Cgas^−/− cells. 12 days later, tumor-bearing mice were injected with 100–200 μCi of ⁶⁸Ga-grazytracer. PET/CT imaging studies were performed at 0.5 h after injection. UMAP, uniform manifold approximation and projection.