FIGURE 2.

Impact of RT on cancer-associated immune cells, endothelial cells and fibroblasts. Tumor irradiation leads to the production and stabilization of HIF-1, which induces Vascular Endothelial Growth Factor (VEGF) production and subsequently endothelial cell proliferation and survival. Endothelial cells increase their membrane expression of α_vβ₃ integrins and adhesion molecules. Those modifications in cell adhesion molecule expression and HIF-1-dependent CXCR-4/SDF-1 release contribute to Bone Marrow Derived Cell (BMDC) recruitment favoring in turn blood vessel stabilization and metastasis formation. RT also activates cancer-associated fibroblasts (CAF) and induces the release of extracellular matrix) (ECM) remodeling enzymes facilitating cell invasion and metastasis formation. NF-κB pathway is activated in irradiated immune cells and regulates the release of numerous cytokines, including TGF-β, an epithelial-to-mesenchymal transition inducer and a CAF activator. On the other hand, induction of inducible Nitric Oxide Synthase (iNOS) expression by tumor-associated macrophages participates to cytotoxic T cell activation and tumor rejection.