Table 1.

Immune-modulatory effects of anti-VEGF TKIs and mAbs in RCC.

Agent	Model or Study Type (Mouse and/or Human)	Effect	Reference
Immune-modulatory effects resulting in reduced immunosuppression of tumour microenvironment
Bevacizumab	Human	Increased tumour infiltration with cytotoxic T cells	[50]
	Human	Increased tumour infiltration with cytotoxic T cells	[57]
	Human	Stimulation of maturation of monocytes into dendritic cells	[59]
	Mouse	Reduced levels of peripheral MDSCs	[60]
Sorafenib	Human	Stimulation of maturation of monocytes into dendritic cells	[59]
Sunitinib	Human	Increased tumour infiltration with cytotoxic T cells	[50]
	Mouse	Reduced levels of MDSCs in the tumour microenvironment	[62]
	Human	Increased tumour infiltration with cytotoxic T cells Reduced levels of MDSCs and regulatory T cells in tumours	[55]
	Human	Reduced peripheral levels of regulatory T cells	[63]
	Human	Reduced levels of MDSCs	[64]
	Human	Increased levels of dendritic cells	[65]
Axitinib	Mouse	Reduced levels of MDSCs in the tumour	[66]
Cabozantinib	Mouse & human	Increased levels of cytotoxic T cells Increased tumour infiltration with lymphocytes Increased cancer cell sensitivity to T cell-mediated killing Reduced levels of regulatory T cells and MDSCs	[56]
	Mouse & human	Reduced expression of PD-L1 on surface of cancer cells Increased cancer cell sensitivity to immune effector cells	[61]
	Human	Reduced expression of PD-L1	[70]
Immune-modulatory effects resulting in increased immunosuppression of tumour microenvironment
Bevacizumab	Human	Increased tumour infiltration with regulatory T cells Increased expression of PD-L1	[50]
	Human	Increased levels of regulatory T cells	[72]
Sunitinib	Human	Increased tumour infiltration with regulatory T cells Increased expression of PD-L1	[50]
	Mouse	Increased tumour infiltration with MDSCs	[73]
Sorafenib	Mouse & human	Reduced migration of dendritic cells Reduced responsiveness of dendritic cells to inflammatory signals Reduced induction of antigen-specific T cells	[74]

Anti-VEGF, anti-vascular endothelial growth factor; mAbs, monoclonal antibodies; MDSC, myeloid-derived suppressor cell; mRCC, metastatic renal cell carcinoma; PD-L1, programmed cell death ligand 1; RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor.