PD-1 and its ligands are important immune checkpoints in cancer

Abstract

// Yinan Dong 1 , Qian Sun 1 and Xinwei Zhang 1 1 Cell Immunology Lab, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of “Cancer Prevention and therapy”, Key Laboratory of Immunology and Cancer Biotherapy, Tianjin, China Correspondence to: Xinwei Zhang, email: // Keywords : PD-1, PD-L1, PD-L2, T cell anergy, immune checkpoint blockade Received : April 14, 2016 Accepted : November 21, 2016 Published : December 10, 2016 Abstract Checkpoint programmed death-1 (PD-1)/programmed cell death ligands (PD-Ls) have been identified as negative immunoregulatory molecules that promote immune evasion of tumor cells. The interaction of PD-1 and PD-Ls inhibits the function of T cells and tumor-infiltrating lymphocytes (TIL) while increasing the function of immunosuppressive regulatory T cells (Tregs). This condition causes the tumor cells to evade immune response. Thus, the blockade of PD-1/PD-L1 enhances anti-tumor immunity by reducing the number and/or the suppressive activity of Tregs and by restoring the activity of effector T cells. Furthermore, some monoclonal antibodies blockading PD-1/PD-Ls axis have achieved good effect and received Food and Drug Administration approval. The role of PD-1/PD-Ls in tumors has been well studied, but little is known on the mechanism by which PD-1 blocks T-cell activation. In this study, we provide a brief overview on the discovery and regulatory mechanism of PD-1 and PD-L1 dysregulation in tumors, as well as the function and signaling pathway of PD-1 and its ligands; their roles in tumor evasion and clinical treatment were also studied.