Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes

Nat Rev Clin Oncol. 2021 Aug;18(8):527-540. doi: 10.1038/s41571-021-00496-y. Epub 2021 Apr 8.

Abstract

Immune checkpoint inhibitors have revolutionized medical oncology, although currently only a subset of patients has a response to such treatment. A compelling body of evidence indicates that anti-angiogenic therapy has the capacity to ameliorate antitumour immunity owing to the inhibition of various immunosuppressive features of angiogenesis. Hence, combinations of anti-angiogenic agents and immunotherapy are currently being tested in >90 clinical trials and 5 such combinations have been approved by the FDA in the past few years. In this Perspective, we describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as the vascular counterpart of immune checkpoints. We review the antitumour immunity-promoting effects of anti-angiogenic agents and provide an update on the current clinical successes achieved when these agents are combined with immune checkpoint inhibitors. Finally, we propose that anti-angiogenic agents are immunotherapies - and vice versa - and discuss future research priorities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Clonal Anergy / drug effects*
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm / immunology
  • Humans
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Treatment Outcome
  • Tumor Escape / drug effects
  • Tumor Escape / physiology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Angiogenesis Inhibitors