Furthermore, mesenchymal cells secrete GM-CSF, which activates TAMs and induces CCL18 production, thereby promoting a positive feedback loop for EMT.34 TAMs actively participate in the formation of the PMN and remodeling of the tumor ECM by secreting proteolytic enzymes (including MMP2 and MMP9) and matrix-associated proteins.159 Additionally, pro-inflammatory factors can further facilitate the establishment of the PMN. This evidence concerns the gene CSF2 and neoplasm.