The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity

• Published in: The Journal of immunology (1950) Vol. 193; no. 8; pp. 3835 - 3841
• Main Authors: Ostrand-Rosenberg, Suzanne, Horn, Lucas A, Haile, Samuel T
• Format: Journal Article
• Language: English
• Published: United States 15.10.2014
• Subjects: Animals; Apoptosis - immunology; B7-1 Antigen - immunology; B7-H1 Antigen - immunology; CD8-Positive T-Lymphocytes - immunology; Fas Ligand Protein - immunology; Humans; Immune Tolerance; Lymphocyte Activation - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Mice; Neoplasms - immunology; Programmed Cell Death 1 Receptor - immunology; Signal Transduction - immunology; Tumor Microenvironment - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401572

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.