Direct and indirect regulation of the tumor immune microenvironment by VEGF.

Abstract

Vascular endothelial growth factor-A (VEGF) is the predominant angiogenic factor that is expressed in solid tumors. Besides its critical function in mediating tumor angiogenesis, multiple studies have demonstrated that VEGF also contributes to tumor immunosuppression. VEGF interferes with immune cell trafficking indirectly by promoting a vascular immune barrier through VEGF receptor (VEGFR) activity on endothelial cells. However, VEGFRs are also expressed on multiple immune cell types, including T cells (effector T cells, Tregs) and myeloid cells (DCs, TAMs, MDSCs), where VEGF can have direct effects on immune cell phenotype and function. Thus, it is not surprising that strategies targeting VEGF/VEGFRs have shown efficacy in alleviating tumor-associated immunosuppression and have been combined with immunotherapies, especially immune checkpoint blockade. In this review, we discuss the direct and indirect effects of VEGF on the immunosuppressive tumor microenvironment with particular focus on the direct regulation of immune cells through VEGFR2 activity. We also summarize preclinical and clinical observations of combining antiangiogenesis agents with immunotherapies for the treatment of solid tumors.

• Authors: Yuqing Zhang, Rolf A Brekken
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 111 Issue 6 Pg. 1269-1286 (06 2022) ISSN: 1938-3673 [Electronic] England
• PMID: 35466428 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: ©2022 Society for Leukocyte Biology.

Chemical References

• Angiogenesis Inhibitors
• Immune Checkpoint Inhibitors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Endothelial Cells
• Humans
• Immune Checkpoint Inhibitors
• Neoplasms (immunology, pathology)
• Tumor Microenvironment
• Vascular Endothelial Growth Factor A