Specific soluble factors within the pancreatic TME have been found to regulate CSCs including Nodal/Activin secretion from pancreatic stellate cells, cationic antimicrobial peptide 18/LL-37 from immune cells, and IFN-stimulated factor 15 (ISG15) from tumor associated macrophages [59, 61, 62]. This evidence concerns the gene ISG15 and neoplasm.