Macrophages change their functional state by responding to signaling molecules in the TME, and secrete various cytokines (such as IL-1β, IL-6, CXCL-8, IL-10, CCL2, and CSF-1) to interact with various types of cells in the TME, thus playing a momentous role in the regulation of tumor invasiveness, metastasis and drug resistance (Galdiero et al., 2018; Lin et al., 2019; Korbecki et al., 2020). This evidence concerns the gene CCL2 and neoplasm.