Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges

Nat Rev Clin Oncol. 2018 May;15(5):325-340. doi: 10.1038/nrclinonc.2018.29. Epub 2018 Mar 6.

Abstract

Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one. Immunotherapy relies on the accumulation and activity of immune effector cells within the TME, and immune responses and vascular normalization seem to be reciprocally regulated. Thus, combining antiangiogenic therapies and immunotherapies might increase the effectiveness of immunotherapy and diminish the risk of immune-related adverse effects. In this Perspective, we outline the roles of VEGF and ANG2 in tumour immune evasion and progression, and discuss the evidence indicating that antiangiogenic agents can normalize the TME. We also suggest ways that antiangiogenic agents can be combined with immune-checkpoint inhibitors to potentially improve patient outcomes, and highlight avenues of future research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Humans
  • Immunotherapy / trends
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Vascular Endothelial Growth Factor A / immunology*
  • Vascular Endothelial Growth Factor A / therapeutic use
  • Vesicular Transport Proteins / immunology*
  • Vesicular Transport Proteins / therapeutic use

Substances

  • Angiogenesis Inhibitors
  • C11orf2 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vesicular Transport Proteins