Table 1B.

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

	PD-1/PD-L1 blockade	Other ICB	Tumor types	Model	Findings (mechanisms)	References
PD-1×TIM-3	PD-1-blocking antibody	TIM-3-blocking antibody	Lung adenocarcinoma	Genetically engineered mouse models of lung cancer: EGFR L858R T790M mutation and CC10 RTTA double-positive mice, KrasG12D mice.	TIM-3 blockade treatment after PD-1 blockade failure significantly improved anti-tumor efficacy and survival. The combination therapy increased IFN-γ production and proliferation of TIM-3+ CD8+ T cells from PD-1-resistant mice, decreased the expression of some tumor-promoting cytokines, such as IL-6 and progranulin.	91
PD-1×TIM-3	Anti-PD1 mAb	Anti-TIM-3 mAb	Hepatocellular carcinoma	BALB/c nude mice bearing with HepG2 cells	The combined blocking exhibited a more significant anti-tumor effect than a single blockade in mice with hepatocellular carcinoma, through increased production of T cell effector cytokines (IFN-γ and TNF-α) and TILs, decreased levels of immunosuppressive cytokines (IL-10 and IL-6) and the amounts of PD-1+TIM-3+CD8+ T cells within the TME.	124
PD-1×TIGIT	Anti-PD-1 mAb	Anti-TIGIT mAb 10D7.G8	Melanoma	CD8+ T lymphocytes from PBMCs obtained from patients	Dual blockades of TIGIT and PD-1 further increased NY-ESO-1-specific CD8+ T cell counts. PD-1 blockade increased TIGIT expression, but TIGIT blockade could not increase PD-1 expression.	136
PD-1×TIGIT	Anti-PD-1 (4 H2)	Anti-TIGIT (clone 4B1 mIgG2 a, depleting isotype)	Glioblastoma	C57 BL/6 J mice with intracranial tumor	Both combined blockade and PD-1 single blockade can establish anti-tumor immune memory. The superior efficacy of combination therapy may be due to increased CD8+ and CD4+ T-cell infiltration, higher IFN-γ and TNF-α production, and reduced tumor-infiltrating dendritic cells.	137