The programmed cell death 1 protein (PD-1, PDCD1, CD279) is a member of the CD28 family of immunoreceptors that regulate T cell activation and immune responses. The PD-1 protein contains an extracellular Ig V domain, a transmembrane domain, and a cytoplasmic tail that includes an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). PD-1 is activated by the cell surface ligands PD-L1 and PD-L2. Upon activation, PD-1 ITIM and ITSM phosphorylation leads to the recruitment of the protein tyrosine phosphatases SHP-1 and SHP-2, which suppress TCR signaling . In addition to activated T cells, PD-1 is expressed in activated B cells and monocytes, although its function in these cell types has not been fully characterized. The PD-1 pathway plays an important role in immune tolerance; however, research studies show that cancer cells often adopt this pathway to escape immune surveillance. Consequently, blockade of PD-1 and its ligands is proving to be a sound strategy for neoplastic intervention.