Figure 1: M2 pro-angiogenic macrophage polarization and tumorassociated macrophage in NSCLC. During tumor insurgence and progression a complex and diversified interplay occurs between tumor cells and stromal, endothelial and innate immune cells within the TUMIC and in particular M2 macrophages and TAMs. Several tumor-derived factors, such as hypoxia, chemokines e.g. CXCL1, CXCL2, IL-8, VEGF or from tumor conditioned myeloid cells, e.g. IL-6, CCL2, VEGF, MMPs, plasmin, and other molecules could play a relevant role in the triggering of the angiogenic switch, contributing to the tumor angiogenesis, lymphangiogenesis, the invasive process, and metastasis.