TY - JOUR
T1 - Direct and indirect regulation of the tumor immune microenvironment by VEGF
AU - Zhang, Yuqing
AU - Brekken, Rolf A.
N1 - Publisher Copyright:
©2022 Society for Leukocyte Biology.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - VEGF
KW - angiogenesis
KW - immune regulation
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85128774107&partnerID=8YFLogxK
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U2 - 10.1002/JLB.5RU0222-082R
DO - 10.1002/JLB.5RU0222-082R
M3 - Review article
C2 - 35466428
AN - SCOPUS:85128774107
SN - 0741-5400
VL - 111
SP - 1269
EP - 1286
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -