Innate immune response
Macrophages typically in ltrate human tumors, where they play an important role in shaping the tumor microenvironment (see Figure 2C). In the early stages of tumor development, tumor- associated macrophages (TAMs) are polarized by IFN-γ to an in ammatory M1 phenotype characterized by tumoricidal activ- ity and IL-12 secretion, which supports NK-cell activation and the development of T helper 1 ( 1) immunity.[81,82] In more advanced stages of tumor development, TAMs are recruited to the tumor microenvironment primarily via monocyte chemoat- tractant protein (CCL2)-induced chemotaxis; they are converted to an M2 phenotype via tumor-derived immunosuppressive cy- tokines, including transforming growth factor (TGF)-β and IL- 10, and promote tissue remodeling and angiogenesis.[83] M2- polarized TAMs are enriched in hypoxic and ischemic areas of tumors, where expression of hypoxia-inducible factor 1α (HIF- 1α) and vascular endothelial growth factor (VEGF