Fig 2: DPEP1-KO mice display features of microsatellite instability in epithelial cells.Representative immunofluorescence images for WT Ads and DPEP1-KO ACAs stained for (A) MSH6 and β-catenin or (B) MSH2 or (C) AQP5 and merged with DAPI staining. Scale bars: 100 μm. Representative images are a result of staining tumors from 2 cohorts described in the Methods, where experiments were done in triplicate from WT (n = 12) and DPEP1-KO (n = 10) tumors.

Fig 3: DPEP1-KO mice present with immune-related features of microsatellite instability.Representative immunofluorescence images for WT Ads and DPEP1-KO ACAs stained for (A) MPO, (B) H3-cit, and (C) CD8 merged with DAPI staining. Scale bars: 100 μm. (D and E) Representative PD-L1 IHC staining for WT Ads and DPEP1-KO ACAs. Scale bars: 150 μm (D) and 50 μm (E and insets in D). Representative images are a result of staining tumors from 2 cohorts described in the Methods, where experiments were done in triplicate from WT (n = 12) and DPEP1-KO (n = 10) tumors.

Fig 4: Mice lacking DPEP1 have an increased tumor burden and exhibit invasive adenocarcinoma and invasive squamous cell carcinoma.(A) Quantification of tumor number per mouse comparing WT (n = 12) and DPEP1-KO (n = 10) mice following a regimen of AOM/DSS. (B) Quantification of total tumor volume per mouse in WT (n = 12) and DPEP1-KO (n = 10) groups. (C) Representative H&E images of WT adenoma (Ad) and DPEP1-KO cancer. Scale bars: 1 mm. (D and E) H&E images of DPEP1-KO tumor shows 2 histological subtypes: (D) adenocarcinoma (ACA) with mucinous features as in the inset from C (left) and invasive features (right); and (E) squamous cell carcinoma (SCC), with related inset showing invasion. Scale bars: 200 μm. Error bars represent SEM. ***P < 0.001 by Wilcoxon-Mann-Whitney test.