Figure 1. Intrinsic anti-tumor and anti-angiogenic functions of type I interferons.

Interferon-α/β (IFN-α/β) has direct effects in tumor cells inducing growth arrest and cell death (left panel). After binding to the heterodimeric IFN-α/β receptor 1 and 2 (IFNAR1/IFNAR2), type I IFNs induce a cascade of intracellular events which culminates in expression of genes whose promoters contain the IFN-stimulated response element (ISRE). In this way, several immuno-regulatory cytokines, cell death factors and proteins related to antiviral response are produced, as well as more IFN-α/β, which in turn affects neighboring cells. In addition, anti-tumor effects of type I IFN may also be a consequence of its anti-angiogenic function, impairing tumor vessel formation and leading to death of tumors by lack of oxygen and nutrients (right panel). IFN-α/β can inhibit the production of angiogenic factors by tumor cells, and also directly affects endothelial cells (EC), inhibiting their proliferation and secretion of factors responsible for EC chemotaxis and remodeling of extracellular matrix. Tyrosine kinase 2 (TYK2), Janus kinase 1 (JAK1), signal transducer and activator of transcription (STAT), IFN-regulatory factor 9 (IRF9), IFN-stimulated gene factor 3 (ISGF3), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-8 (IL-8), platelet endothelial cell adhesion molecule-1 (PECAM-1), promyelocytic leukemia protein (PML), matrix metalloproteinase 9 (MMP9).