dMMR tumor intrinsic cGAS–IFN upregulates the expression of Trex1 to dominate tumor escaping immunosurveillance. (A) C57BL/6 mice (n = 5) were transplanted s.c. with 2 × 10⁶ MC38 WT or MC38-Trex1^−/− cells and treated with IgG or anti-IFNaR1 antibody (200 µg/mouse). (B) C57BL/6 mice (n = 5) were transplanted s.c. with 2 × 10⁶ MC38 WT, Trex1^−/−, Ifnar1^−/−, or Ifnar1^−/−Trex1^−/− cells. (C) C57BL/6 WT mice and Ifnar1^−/− mice (n = 4) were transplanted s.c. with 2 × 10⁶ MC38 WT or MC38-Trex1^−/− cells. (D) C57BL/6 WT mice and Batf3^−/− mice (n = 4) were transplanted s.c. with 2 × 10⁶ MC38-Trex1^−/− cells. (E) C57BL/6 mice (n = 4–5) were transplanted s.c. with 1 × 10⁷ MC38, MC38-Trex1^−/−, MC38-Cgas^−/−, and MC38-Trex1^−/−Cgas^−/− cells. 5 days later, tumor tissues were collected for Ifnb1 mRNA detection by RT-qPCR. (F) MC38 cells (n = 3/group) were collected, and MHC I expression was analyzed by flow cytometry. (G) WT and Sting^−/− C57BL/6 mice (n = 5) were transplanted s.c. with 2 × 10⁶ MC38 WT or MC38-Trex1^−/− cells. (H) C57BL/6 mice (n = 5) were transplanted s.c. with 2 × 10⁶ MC38, MC38-Trex1^−/−, MC38-Cgas^−/−, and MC38-Trex1^−/−Cgas^−/− cells. (I) BALB/c mice (n = 4) were transplanted s.c. with 5 × 10⁵ 4T1, 4T1-Trex1^−/−, 4T1-Mlh1^−/− (day 108), 4T1-Mlh1^−/−Trex1^−/− (day 108), 4T1-Mlh1^−/−Sting^−/− (day 110), 4T1-Sting^−/−Trex1^−/−, and 4T1-Mlh1^−/−Sting^−/−Trex1^−/− (day 110) cells. Data indicate mean ± SEM and are representative of (A–I) independent experiments. The statistical analysis was performed by two-way ANOVA in A–D and H–I and unpaired Student’s two-tailed t test in E and F. NS, not significant, *P < 0.05, **P < 0.01, and ****P < 0.0001. MFI, mean fluorescence intensity.