Table 1.

Checkpoint molecules and their ligands.

	Expressed on	Ligates	Effect	Checkpoint inhibitors	References
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4 or CD152)	T Cells	CD28, CD80 (B7-1) and CD86 (B7-2) on APCs	T cells secrete less IL-2, preventing T cell expansion and limiting T cell responses	Ipilimumab (Yervoy). Response rates 11.1% to 28.5% in late stage melanoma	37-39
Programmed cell death (PD-1)	T cells and pro-B cells	PD-L1 (CD274 or B7 homolog 1, B7-H1) and PD-L2 (B7-DC) on tumor cells and APCs	Increased apoptosis of effector CTLs	Pembrolizumab (Keytruda) and nivolumab (Opdivo). Response rates in metastatic melanoma of 25–41% for nivolumab, and 26–43% for pembrolizumab PD-L1 inhibitors (e.g., MPDL3280A and MEDI4736) are in developmental and trial stages with encouraging results	43-47 clinicaltrials.gov identifier: NCT01295827.
T cell immunoglobulin and mucin protein-3 (TIM-3, also known as Hepatitis A virus cellular receptor 2 or HAVCR2, and CD366)	Activated Th-1 cells	Unknown Putative ligand, beta-galactoside binding lectin-9 (Gal-9), expressed in many tissues and on many cell types including immune, epithelial and endothelial cells	Th-1 cell apoptosis to prevent autoimmune responses The Gal-9-TIM-3 pathway suppresses Th-1 and Th-17 cells, leading to decreased production of IFNγ, IL-2, IL-6 and IL-17	In pre-clinical development	54-62