Table 1D.

The preclinical studies of the combination of PD-1/PD-L1 blockade with other ICBs in cancer therapy

Targets	PD-1/PD-L1 blockade	Other ICB	Tumor types	Model	Findings (mechanisms)	References
PD-L1×CD47	IBI322 (CD47/PD-L1 bispecific antibody)	Burkitt's lymphoma, melanoma		NOD-SCID mouse bearing with Raji-PDL1 cell or A375 cells	CD47 and PD-L1 bispecific antibody (IBI322) was found to exhibit lower toxicity reactions and synergistic anti-tumor effects via increasing IFN-γ levels and promoting phagocytosis of macrophages.	193
PD-L1×CD47	Anti-PD-L1 mAb	SIRPα-Fc	B-cell lymphoma	BALB/c mice with lymphoma	Dual blockade with anti-CD47 and anti-PD-L1 therapy activated CD8+ T cells, increased the secretion of perforin, granzyme B and IFN-γ, and enhanced macrophage infiltration.	162
PD-1×A2AR	RMP1-14 (anti-PD-1 mAb)	SCH58261	Breast carcinoma	C57BL/6 and BALB/C mice bearing with MC38 cells and 4T1.2 cells	Blocking PD-1 upregulated A2AR expression on CD8+ TILs. The combination blockade of PD-1 and A2AR increased the production of IFN-γ by tumor-infiltrating CD8+ T cells both in vitro and in vivo.	168
PD-1×A2AR	Anti-PD-1 mAb (RMP1-14, Bioxcell)	CPI-444 (A2AR antagonist)	Colon cancer, melanoma	C57BL/6 mice bearing with MC38 cells and B16-OVA cells	CPI-444 moderately suppressed tumor growth, while combined with anti-PD-1 showed significant anti-tumor efficacy in vivo (causing tumor regression and improving survival), which might be related to the inhibition of PD-1 and LAG-3 expression by CPI-444 on CD8+ T cells and Tregs.	170