Fig. 3

KL tumors had excessive collagen deposition and collagen blocks T cell infiltration into tumor nest. A GO analysis for significantly upregulated genes in KL tumors compared to KP tumors. Representative and related GO signal pathways among top 30 upregulated pathways were listed here. B Reactome analysis for significantly upregulated genes in KL tumors compared to KP tumors. Representative and related Reactome signal pathways among top 20 upregulated pathways were listed here. C GSEA analysis for ECM-receptor interaction and GAP junction in KL and KP tumors. D Heatmap of RNA-seq showing collagen-related genes statistically significant (FDR < 0.05) differentially expressed in KL subcutaneous tumors. E Representative images and quantification of area performed by Masson, Siruis Red, Collagen I and Collagen III. Unpaired Student’s t-test was used to compare the statistical significance between two groups. Scale bars, 100 μm. inset scale bars, 50 μm. F Representative images showing spatial relations between collagen deposition and CD8⁺TILs infiltration. Scale bars, 100 μm. inset scale bars, 20 μm. G Representative images and quantification of CD8⁺TILs infiltrated in tumor nest and stroma in two groups. Scale bars, 100 μm. Results in each group were presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, and ^nsp-values with no statistical difference. KL, KRAS^G12DLKB1^−/−; KP, KRAS^G12DTP53^−/−; BP, biological process; CC, cellular component; MF, molecular function; ECM, extracelluar matrix; TIL, tumor infiltrating lymphocyte; SEM, standard error of mean