Figure 2.

Setd2 loss in pancreatic tumor promotes the recruitment and immunosuppressive phenotype of neutrophils. A) Neutrophil chemotaxis assay using 20% conditioned medium from Setd2 ^WT or Setd2 ^KO pancreatic tumor cells. Representative flow cytometry plots and statistical analysis are shown (n = 3). B,C) Orthotopic Setd2 ^WT and Setd2 ^KO tumor‐bearing mice were administered CXCR2 antagonist (CXCR2i, SB225002, 1 mg kg⁻¹ every other day) and DMSO as a control for 12 days. B) Pancreatic tissues were collected for H&E staining. C) Quantification of lesion area and percentage of infiltrating neutrophils from the indicated mice (n = 4 per group). Scale bar = 2 mm. D) Neutrophils sorted from bone marrow (BM) were treated with conditioned medium from Setd2 ^WT or Setd2 ^KO cells, as well as control medium for 24 h. The above‐primed neutrophils were collected for RNA‐seq. Principal component analysis (PCA) scores plot indicating discrimination among Neu‐Cont, Neu‐Setd2 ^WT, and Neu‐Setd2 ^KO (n = 3 per groups). E) Heatmap of RNA‐Seq data to compare the gene expression among the Neu‐Cont, Neu‐Setd2 ^WT, and Neu‐Setd2 ^KO groups. F–I) Pathway enrichment of the indicated gene cluster based on RNA‐Seq data. The experiments had three replicates and were repeated three times (A). Data are represented as the mean ± SD (A) or mean ± SEM (C). Statistical differences were determined with unpaired Student's t test in (A), and one‐way ANOVA and Tukey's multiple comparisons test in (C).