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

Anti-angiogenic therapy has the capacity to ameliorate antitumour immunity and, thus, some combinations of anti-angiogenics and immunotherapies have been approved and a number of them are being tested. The authors of this Perspective describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as a vascular counterpart of immune checkpoints. 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.

Automated summary

Anti-angiogenic therapy has the potential to enhance antitumor immunity by inhibiting immunosuppressive features of angiogenesis. Combinations of anti-angiogenic agents and immunotherapy have shown success in clinical trials and have been approved by the FDA. The article discusses the impact of angiogenesis on antitumor immunity, the role of endothelial cells, and the progress in combining anti-angiogenic agents with immune checkpoint inhibitors.