For instance, the involvement of mixed M1/M2, GM-CSF-stimulated macrophages in a tumour-promoting loop challenges the view of tumour-permissive macrophages as polarized M2 mononuclear phagocytes and hints at contexts in which pro-inflammatory microenvironments may allow effective tumour-promoting activities through mediators such as GM-CSF and HB-EGF. This evidence concerns the gene HBEGF and neoplasm.