Mechanistically, we revealed that SETD2‐H3K36me3 loss directly downregulated Cxadr expression in pancreatic tumor cells, allowing for PI3K‐AKT activation and the release of excessive CXCL1 and GM‐CSF, which attracted neutrophils and reprogrammed them toward an immunosuppressive phenotype. This evidence concerns the gene CXCL1 and pancreatic neoplasm.