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

Zowi R. Huinen, Elisabeth J. M. Huijbers, Judy R. van Beijnum, Patrycja Nowak-Sliwinska*, Arjan W. Griffioen*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)527-540
Number of pages14
JournalNature Reviews Clinical Oncology
Issue number8
Early online date2021
Publication statusPublished - Aug 2021

Cite this