Fig. 1

The origin and polarization of TAMs in tumor microenvironments. Recruited macrophages from blood (green) and tissue-resident macrophages from the yolk sac (purple) coexist in tumors. Recruited macrophages represent the majority of TAMs. Peripheral blood monocytes are recruited locally and differentiate into macrophages in response to various chemokines and growth factors produced by stromal and tumor cells in the tumor microenvironment (CCL2, CSF1, VEGFA, CCL18, CCL20, and CXCL12). Factors that promote the polarization of TAMs to a protumor phenotype can be subdivided into those actively produced by tumor cells (microparticles, CCL2/3/4, CSF1, IL-4, IL-10), those derived from immune system components (Treg-derived IL-10, B cell-derived Igs, Th2-derived IL-4/13, and MSC-derived MFG-E8), those secreted by TAMs (MIF, IL-10, CXCL12), and those resulting from tissue stress (hypoxia, tumor-derived HMGB-1, ECM components) (orange). In addition, TAMs can also be differentiated from myeloid-derived suppressor cells in the leukemic stem cell niche