TABLE 1.

Summarized regulation of tumor immune microenvironment by antiangiogenic therapy

Agent	Target	Effects of antiangiogenic therapy	References
Smallmolecule tyrosine kinase inhibitor
Sunitinib	VEGFRs, c-Kit, PDGFR, Flt-3, RET, CSF-1R	Up-regulates CXCL10, CXCL11 in tumor vasculature; reduces Tregs; increases blood myeloid DCs; decreases MDSCs; reduces Treg and type 1 T-cell suppression	[34][76][78][106][131][132][136]
Sorafenib	VEGFRs, c-Kit, PDGFR, RAF-kinases, RET	Inhibits DCs function; promotes DCs differentiation and activation.	[76][77]
Axitinib	VEGFRs, c-Kit, PDGFR	Suppresses TIM-3 expression on T cells; decreases suppressive capacity of MDSCs; leads to the dysfunction of DCs	[53][135][79]
Apatinib	VEGFR2, c-Kit, c-SRC	Limits the recruitment of TAMs	[109]
Monoclonal antibody
Bevacizumab	VEGF-A	Increases the infiltration of proliferating CD8+ T cells; reduces Treg recruitment and decreases the proportion of Ki67+ Tregs; reduces MDSCs; promotes differentiation of DCs	[54][59][61][62][80][106]
A2V	VEGF-A, ANGPT2	Up-regulates CXCL10, VCAM-1, and PD-L1 on blood vessels; reprograms TAMs; suppresses tumor growth	[35][115][116]
DC101	VEGFR2	Promotes T cells infiltration; polarizes TAMs from M2 to M1; decreases suppressive capacity of MDSCs	[40][134]
r84/mcr84	VEGF-A	Decreases FasL in tumor vasculature; increases CD8+ T cells infiltration; decreases MDSCs; decreases PD-L1 expression on MDSCs.	[39][106][131]
B20.4.1.1	VEGF-A	Increases antigen-specific response of CD8+ T cells	[51]
Ramucirumab	VEGFR2	Increases CD8+ T-cell infiltration; reduces PD-1 expression on CD8+ T cells; reduces Tregs	[55]

Abbreviations: DCs, dendritic cells; M1, proinflammatory macrophage; M2, anti-inflammatory macrophage; MDSC, myeloid-derived suppressor cell; TAM, tumor-associated macrophage; Treg, regulatory T cell.