Programmed death-1/programmed death-1 ligand axis as a therapeutic target in oncology: current insights

Over the past few years, the functional modulation of immune-checkpoint pathways using monoclonal antibodies has emerged as a promising anticancer therapeutic strategy. A key mechanism utilized by tumor cells to induce immune tolerance is upregulation of the programmed death-1 (PD-1) pathway. PD-1 is a negative coregulatory receptor on T-cells and antigen-presenting cells. The PD-1 ligand (PD-L1) is expressed by several tumor types, and appears to be dynamically regulated by the immune microenvironment. Several investigational agents targeting either PD-1 or PD-L1 are under clinical development and show durable antitumor activity across several tumor types. This review summarizes the conceptual basis, safety, and clinical activity of currently available PD-1 pathway therapeutic antibodies.