Table 1.

Immune checkpoint proteins, their receptors and/or ligands and their main functions.

ICPs	Cellular Source	Ligands/Receptors	Main Functions	References
PD-1	Activated T cells	PD-L1/PD-L2	1. Blocking the interaction between PD-1 and its ligand. 2. Reducing cytokine secretion.	(15, 41, 42)
PD-L1	DCs, MDSCs, Macrophages	PD-1	Inhibiting T cell responses	(43–45)
CTLA-4	Tregs	CD80/86	Inhibiting T cell responses	(15, 46)
PVRIG	DCs, Th1 cells, NK cells	CD112	Inhibiting T cell responses	(47–50)
TIM-3	DCs, NK cells, Th1 cells, Th17 cells, Macrophages	GAL-9, PS	Inhibiting Th responses	(51–54)
GAL-9	Eosinophils, DCs, T cells, Macrophages, Lymphoid cells, Kupffer cells, intestinal epithelial cells, vascular endothelial cells	TIM-3	Regulating immune homeostasis	(55–57)
VISTA	T cells, APCs	NA	Inhibiting T cell responses	(58–60)
LAG3 (CD223)	Plasmacytoid DCs (pDCs), NK T cells, Tregs	MHC-II, GAL-9, FGL1	lnteracting with MHC-II	(61–63)
TIGIT	T cells, NK cells	CD155, CD112	Supressing anti-tumor immunity	(64–66)
CD40	B cells, DCs, hematopoietic progenitor cells	CD154	Activating NF-κB, MAPKs, PI3, JAK3-STAT5 signaling pathways.	(67–69)
CD70	Activated T cells, mature DCs, B cells	CD27	1. Stimulating T cell differentiation. 2. Enhancing cytotoxic T cell activity. 3. Promoting TNF-α production. 4. Activating B cells.	(70–73)
CD47	RBCs, non-hematopoietic cells	SIRPα, TSP-1, Integrins	1. Activating SHP-1 and SHP-2 pathways. 2. Inhibiting macrophage activity.	(74–76)

SHP1/2, Src-homology 2 domain (SH2)-containing protein tyrosine phosphatase.