title: Vascular normalization as an emerging strategy to enhance cancer immunotherapy.
abstract: The recent approval of Provenge has brought new hope for anticancer vaccine therapies. However, the immunosuppressive tumor microenvironment seems to impair the efficacy of vaccine therapies. The abnormal tumor vasculature creates a hypoxic microenvironment that polarizes inflammatory cells toward immune suppression. Moreover, tumors systemically alter immune cells' proliferation, differentiation, and function via secretion of growth factors and cytokines. For example, VEGF, a major proangiogenic cytokine induced by hypoxia, plays a critical role in immunosuppression via these mechanisms. Hence, antiangiogenic treatment may be an effective modality to potentiate immunotherapy. Here, we discuss the local and systemic effects of VEGF on tumor immunity and propose a potentially translatable strategy to re-engineer the tumor-immune microenvironment and improve cancer immunotherapy by using lower "vascular normalizing" doses of antiangiogenic agents.
authors: Edwin L. Steele Laboratory of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors: Yuhui
authors: Y
authors: Huang
authors: Shom
authors: S
authors: Goel
authors: Dan G
authors: DG
authors: Duda
authors: Dai
authors: D
authors: Fukumura
authors: Rakesh K
authors: RK
authors: Jain
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D009369:Neoplasms / Q000098:blood supply* / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A