Table 1. Synergistic effect of combination immunotherapy with PD-1/PD-L1 antibody and anti-VEGF/TKI.

	PD-1/PD-L1 antibody monotherapy	PD-1/PD-L1 antibody plus anti-VEGF/TKI combination immunotherapy
Mode of action	PD-1･PD-L1 blockade	PD-1･PD-L1 blockade
		Direct antitumor effect by inhibiting signaling pathway
		Increased cancer antigen release by tumor necrosis
		Increased antigen presentation by maturation of dendritic cell
		Increased activation of CD8+ T cell at the priming phase
		Increased tumor infiltration of CD8+ T cell by normalization of abnormal tumor vessel
		Improvement of tumor microenvironment from immune suppressive to immune responsive

VEGF, vascular endothelial growth factor; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; TKI, tyrosine kinase inhibitor.