Figure 1.

Role of tumor-associated myeloid cells in cancer cells survival, proliferation and migration. During tumorigenesis various myeloid cells populations, including: dendritic cells (DC), myeloid-derived suppressor cells (MDSC), macrophages, neutrophils, eosinophils, basophils, and mast cells can support cancer cells survival, proliferation, and migration. These processes can be stimulated by direct effect on tumoral cells or indirectly by influencing tumor microenvironment (TME), including extracellular matrix (ECM) remodeling and angiogenesis stimulation. Direct effects are mediated through production of interleukin IL-6, IL-8, IL-17, IL-22, IL-23, prostaglandin E2 (PGE2), transforming growth factor beta (TGF-β), vascular endothelial growth factor A (VEGF-A), osteopontin, and tumor necrosis factor α (TNF-α). Neutrophils secrete the iron-transporting protein transferrin which is a major mitogen for tumor cells and release of neutrophil extracellular traps (NET), including their deoxyribonucleic acid (DNA). Neutrophils produce neutrophil elastase favoring tumor cell proliferation and regulate the HMGB1/RAGE/IL-8 axis favoring the crosstalk between glioma cells and the TME. Mast cells release tryptase and IL-1 beta (IL1-β) mediating malignant pleural effusion. Basophils express Fcε Receptor I, promoting their tissue infiltration and producing cysteinyl leukotrienes (CysLT), allowing for proangiogenic activity of activated basophils. DC express OX40, Siglec-10, leukocyte immunoglobulin-like receptor B1 (LILRB1), and SIRPα, which, respectively, recognize OX40 ligand (OX40L), CD24, MHC class I-associated β2M subunits, and CD47 at the surface of tumor cells blocking phagocytosis. Macrophages are an important source of various metalloproteinases (MMPs, MMP2, 7, 9) and cathepsins that provide conduits for tumor cells in the extracellular matrix (ECM). VEGF that is produced by myeloid cells is a major stimulator of angiogenesis.