title: Antagonists of PD-1 and PD-L1 in Cancer Treatment.
abstract: The PD-1 pathway, comprising the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates local immunosuppression in the tumor microenvironment. Drugs designed to block PD-1 or PD-L1 "release the brakes" on anti-tumor immunity and have demonstrated clinical activity in several types of advanced cancers, validating this pathway as a target for cancer therapy. Two such drugs have recently been approved to treat melanoma and lung cancers, and regulatory approvals in first- and second-line settings for additional cancer types are anticipated. The manageable safety profile of PD-1/PD-L1 blocking drugs identifies them as suitable for outpatient administration and the development of combinatorial therapies. Ongoing studies aim to identify biomarkers to guide patient selection, which would further improve the risk:benefit ratio for these drugs.
authors: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Evan J
authors: EJ
authors: Lipson
authors: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Patrick M
authors: PM
authors: Forde
authors: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Hans-Joerg
authors: HJ
authors: Hammers
authors: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Leisha A
authors: LA
authors: Emens
authors: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Dermatology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Janis M
authors: JM
authors: Taube
authors: Department of Surgery, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
authors: Suzanne L
authors: SL
authors: Topalian
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor