Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response

Int J Mol Sci. 2021 May 4;22(9):4871. doi: 10.3390/ijms22094871.

Abstract

During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.

Keywords: angiogenesis; cancer; immune response; vascular endothelial growth factor.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab / therapeutic use
  • Capillary Permeability / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Endothelial Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunity, Innate / drug effects
  • Immunologic Factors / therapeutic use*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Ramucirumab
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / therapeutic use
  • Signal Transduction
  • Sorafenib / therapeutic use
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / immunology

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Bevacizumab
  • Sorafenib
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1