Fig 2: Immune cell and endothelial cell heterogeneity.a UMAP including CD45-positive cells. Time points post-tamoxifen injection (PTI) and cell numbers are presented on the right. b The same UMAP as in (a), the number of each cluster is indicated. c Dot plot of selected differentially expressed genes in macrophages; in early time point PTI, late time point PTI and tumor-associated macrophages. Dot size represents the scaled expression level and color represents the percentage of expressed cells. d Violin plot of cells in cluster I_24 (which we identify as neutrophils) and cells from all other CD45-positive clusters. Markers of macrophages and neutrophils are shown. Expression levels on the y-axis—normalized expression. e Violin plot showing the expression level of selected genes that are expressed in CD3-positive cells. Clusters I_2, I_11, and I_22 include CD8-positive T cells. Clusters I_9, I_15, I_16, I_19, I_20, include CD4-positive T cells. f UMAP includes CD31-positive cells. Time points post-tamoxifen injection and cell numbers are presented on the right. g The same UMAP as in (f), the number of each cluster is indicated. h The average expression level of selected differentially expressed genes of endothelial cells, between early time point PTI and late time point. Expression scale is indicated on the right and gene annotation on the top. i Potential interactions between endothelial cells and immune cells. Scaled gene expression of selected adhesion molecules, cytokines and chemokines and their matched receptors are shown. Blue lines show the potential interactions. Left heat map includes endothelial scaled expressed genes as indicated in endothelial cells clusters. Average of all the early time point PTI clusters or individual late time point PTI clusters as listed on the bottom. Right heat map includes expression levels of genes that encode matched receptors in immune cells as indicated on the bottom. Red - high expression, blue - low expression (see bars).

Fig 3: FAP inhibition does not modify T cell infiltration and suppresses cell proliferation in Mdr2−/− mice. (A–C), Representative images and quantification of CD3- and Ki67-positive cells in 10 random fields (×200) from the central right lobe of each liver. Data in (B–C) are means ± standard error of the means (SEMs). Statistical analysis was performed as detailed in Figure 1.

Fig 4: Status of T and B lymphocytes in base-edited monkeys. a–d Immunohistochemistry was performed to assess the presence of IgM+ and CD3+ cells in the thymus (a, b) and spleen (c, d). Quantitative analysis was conducted on WT and mutant monkeys. Statistical analysis of the data was carried out using an unpaired two-tailed t-test to compare the two groups. A significance level of P < 0.05 was considered statistically significant. Each experiment was repeated three times. Scale bars: 20 µm. e Representative flow cytometry results of peripheral blood lymphocytes in WT and mutant monkeys

Fig 5: Single-cell RNA-seq experiment of pancreatic tissue, taken from Ptf1a-CreER, LSL-Kras G12D, LSL-tdTomato mice at different time points post-tamoxifen injection (PTI).a–h The accumulation of duct-like structures and PanINs at different time points post-tamoxifen injection (PTI). Hematoxylin and Eosin (H&E) staining of histological sections of mice pancreas. The time point PTI is indicated above each panel. Based on the number of PanINs and duct-like structures (quantification in Supplementary Fig. 1a), we define early stage, late-stage and tumor sample. g, h Two sections from the same mice, g tumor adjacent tissue, and h tumor tissue. In early stage samples, lesions were rare. Scale bars 200 µm. i Pancreatic tissues from mice were dissected and single-cell RNA-seq experiments were performed. Uniform manifold approximation and projection (Umap) includes all cells from seven different time points PTI. The data were produced from nine mice, two mice from 3 months PTI, two mice from 5 months PTI and one mouse from each of the other time points. Time points are indicated on the right side of the panel, the number of cells is shown in parentheses. Cell types were determined based on the expression level of representative markers as indicated in Supplementary Fig. 1. j, k Immunostaining of pancreatic sections using anti-CD3 antibody. Both sections were taken from five months PTI mice, j control mouse Ptf1a-CreER, LSL-tdTomato (PT), k Ptf1a-CreER, LSL-Kras G12D, LSL-tdTomato (PRT) mouse. Scale bars 100 µm. l, m Immunostaining of pancreatic section using anti-F4/80 antibody. Both sections were taken from 5 months PTI mice, l control mouse Ptf1a-CreER, LSL-tdTomato (PT), m Ptf1a-CreER, LSL-Kras G12D, LSL-tdTomato (PRT) mouse. Scale bars 200 µm.