title: The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity.
abstract: Programmed death ligand 1 (PD-L1, also known as B7 homolog 1 or CD274) is a major obstacle to antitumor immunity because it tolerizes/anergizes tumor-reactive T cells by binding to its receptor programmed death-1 (CD279), renders tumor cells resistant to CD8(+) T cell- and FasL-mediated lysis, and tolerizes T cells by reverse signaling through T cell-expressed CD80. PD-L1 is abundant in the tumor microenvironment, where it is expressed by many malignant cells, as well as by immune cells and vascular endothelial cells. The critical role of PD-L1 in obstructing antitumor immunity has been demonstrated in multiple animal models and in recent clinical trials. This article reviews the mechanisms by which PD-L1 impairs antitumor immunity and discusses established and experimental strategies for maintaining T cell activation in the presence of PD-L1-expressing cells in the tumor microenvironment.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250 srosenbe@umbc.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250.
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Horn
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Haile
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D053222:Fas Ligand Protein; D061026:Programmed Cell Death 1 Receptor