title: Programmed death-1 & its ligands: promising targets for cancer immunotherapy.
abstract: Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Shrimali
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: Rasha
authors.initials: R
authors.lastname: Abu-Eid
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: Mikayel
authors.initials: M
authors.lastname: Mkrtichyan
authors.affiliation: Georgia Regents University Cancer Center, Augusta, GA 30912, USA.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: PD-1 receptor; PD-L1; PD-ligands; combination cancer immunotherapy; immune escape; immune inhibitory pathway