title: Pools of programmed death-ligand within the oral cavity tumor microenvironment: Variable alteration by targeted therapies.
abstract: Enhanced understanding of programmed death-ligand (PD-L) expression in oral cancer is important for establishing rational combinations of emerging immune checkpoint and molecular targeted therapies.
  
  
  
  We assessed PD-L and interferon (IFN) expression in immunogenic murine oral cancer-1 (MOC1) and poorly immunogenic MOC2 cell models after treatment with mammalian target of rapamycin (mTOR) and MEK1/2 small molecule inhibitors in vitro and in vivo.
  
  
  
  PD-L1 but not PD-L2 is expressed on MOC1 and 2 cells and is type I and II IFN-dependent. PD-L1 is differentially expressed on cancer and endothelial cells and infiltrating myeloid-derived suppressor cells, macrophages, and regulatory T cells (Tregs) in highly and poorly immunogenic tumors. PD-L1 expression is variably altered after treatment with inhibitors in vivo, with an imperfect relationship to alterations in IFN levels in the tumor microenvironment.
  
  
  
  PD-L1 expressed on cancer and infiltrating immune cells is variably altered by targeted therapies and may, in part, reflect changes in tumor IFN. © 2016 Wiley Periodicals, Inc. Head Neck 38:1176-1186, 2016.
authors.affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institutes of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
authors.forename: Sujay
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Andria
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institutes of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
authors.forename: Harrison
authors.initials: H
authors.lastname: Cash
authors.affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institutes of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
authors.forename: Carter Van
authors.initials: CV
authors.lastname: Waes
authors.affiliation: Tumor Biology Section, Head and Neck Surgery Branch, National Institutes of Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.|Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Clint T
authors.initials: CT
authors.lastname: Allen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy / Q000379:methods*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D061026:Programmed Cell Death 1 Receptor / Q000187:drug effects / Q000235:genetics*; D011897:Random Allocation; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics
chemical_list: D061026:Programmed Cell Death 1 Receptor; D007372:Interferons
keywords: interferon; oral cancer; programmed death; targeted therapy