title: Harnessing the power of the immune system via blockade of PD-1 and PD-L1: a promising new anticancer strategy.
abstract: Cancer cells employ several mechanisms to evade the immune system of their host, thus escaping immune recognition and elimination. Of particular interest is a cancer cell's ability to co-opt the immune system's innate ligands and inhibitory receptors (also known as checkpoints), thus creating an immunosuppressive microenvironment that downregulates T-cell activation and cell signaling. The recent development of the checkpoint inhibitors anti-programmed death-1 and anti-programmed death ligand-1 has generated an enormous amount of interest as a potential new anticancer strategy in solid tumors, particularly in non-small-cell lung cancer, renal cell carcinoma and melanoma. Data suggest significant disease response rates using anti-programmed death-1 and anti-programmed death ligand-1 antibodies, even in heavily pretreated patients. Future directions include optimization of drug delivery sequence and combination of immunotherapy with other therapies including cytotoxic chemotherapy, radiation, antiangiogenic agents and small-molecule tyrosine kinase inhibitors.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Cancer Research Building I, Room 186, 401 North Broadway Street, Baltimore, MD 21287, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Reiss
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Forde
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor