Deletion of MSI-H/dMMR tumors endogenous TREX1 specifically enhances IFN response. (A) Heatmap of the normalized abundances of signals in four groups from RNA-seq data. (B) The 3D dot map showed that the 4T1-Trex1^−/−Mlh1^−/− (day 90) cells expressed significantly different genes than the other three groups. Red represents genes that are significantly upregulated by 4T1-Trex1^−/−Mlh1^−/− compared with the other three groups, and blue represents genes that are significantly downregulated. (C) The signal pathway enrichment results of significantly upregulated genes in 4T1-Trex1^–/–Mlh1^–/– (day 90) vs. other groups; the point color indicates the rich factor, and the point size indicates the upregulated gene count in each signal pathway. (D) The heatmap of ISGs and antigen presentation-related genes in four groups from RNA-seq data. (E) The GSEA enrichment result of upregulated genes from 4T1 DKO (day 90) vs. 4T1-Mlh1^−/− (day 90) and 4T1-Trex1^−/− vs. 4T1 WT. (F) 4T1 cells (n = 3/group) were collected for Ifnb1 mRNA detection by RT-qPCR. (G) 4T1, 4T1-Mlh1^−/− (day 93) cells (n = 3/group) were collected, and MHC I expression was analyzed by flow cytometry. (H) MC38 cells (n = 3/group) were collected, and MHC I expression was analyzed by flow cytometry. Data are shown as mean ± SEM and are representative of three (F–H) independent experiments. The statistical analysis was performed by unpaired Student’s two-tailed t test in F–H. NS, not significant, ****P < 0.0001. MFI, mean fluorescence intensity.