Table 1.

Potential immune checkpoint receptor targets for genome editing in the context of cancer adoptive cellular therapies.

	Name (gene)	Function	Ligand	Intra-cellular signaling/second messengers	Recognition motif	References
Co-inhibitory receptors	PD-1 (CD279)	Inhibition of T-cell activation and promotion of tolerance	PD-L1 (B7-H1)	SHP-1	ITIM	Keir et al. (56), Parry et al. (57)
			PD-L2 (B7-DC)	SHP-2	ITSM
	LAG-3 (CD223)	Down regulation of T-cell cytokine secretion and proliferation	MHCII	–	–	Pardoll (12), Turnis et al. (58)
	BTLA (CD272)	Suppression of T-cell response	HVEM	SHP-2	ITIM	Murphy et al. (59), Watanabe et al. (60)
	OX2R (CD200R)	Inhibits T-cell function	CD200	DOK2	NPxY	Kretz-Rommel et al. (61), Moreaux et al. (62), Pallasch et al. (63)
	TIM-3	Down regulation of T-cell cytokine secretion and proliferation	Galectin 9	–	–	Pardoll (12), Zhu et al. (64)
			Phosphatidylserine
	TIGIT	Inhibition of T-cell activation	VR, PVRL2, and PVRL3	–	ITIM	Joller et al. (65)
	LAIR-1	Inhibits cytotoxic activity	Collagen	SHP-1	ITIM	Lebbink et al. (66), Meyaard (67)
				SHP-2
Receptors for soluble regulatory mediators	PGE2 receptors EP2/4	Inhibition of T-cell activity	PGE2	Adenylyl cyclase	–	Mahic et al. (68), Oberprieler et al. (53)
				cAMP
	Adenosine receptor 2A (A2AR)	Blocks T-cell activity	Adenosine	Adenylyl cyclase cAMP	–	Pardoll (12), Ohta et al. (50), Raskovalova et al. (69)

Non-extensive list of immune checkpoint receptors known to impair anti-tumor T-cell immunity in a cell-intrinsic manner. The relevant intra-cellular signaling and second messenger pathways, when known, are indicated.