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PD-1 is a 50-55 kD member of the B7 Ig superfamily. PD-1 is also a member of the extended CD28/CTLA-4 family of T cell regulators and is suspected to play a role in lymphocyte clonal selection and peripheral tolerance. The ligands of PD-1 are PD-L1 and PD-L2, and are also members of the B7 Ig superfamily. PD-1 and its ligands negatively regulate immune responses. PD-L1, or B7-Homolog 1, is a 40 kD type I transmembrane protein that has been reported to costimulate T cell growth and cytokine production. The interaction of PD-1 with its ligand PD-L1 is critical in the inhibition of T cell responses that include T cell proliferation and cytokine production. PD-L1 has increased expression in several cancers. Inhibition of the interaction between PD-1 and PD-L1 can serve as an immune checkpoint blockade by improving T-cell responses In vitro and mediating preclinical antitumor activity. Within the field of checkpoint inhibition, combination therapy using anti-PD1 in conjunction with anti-CTLA4 has significant therapeutic potential for tumor treatments. PD-L2 is a 25 kD type I transmembrane ligand of PD-1. Via PD-1, PD-L2 can serve as a co-inhibitor of T cell functions. Regulation of T cell responses, including enhanced T cell proliferation and cytokine production, can result from mAbs that block the PD-L2 and PD-1 interaction.