title: Programmed death ligand 1 is expressed in canine B cell lymphoma and downregulated by MEK inhibitors.
abstract: Programmed death ligand 1 (PD-L1) expression in antigen-presenting cells and tumors can inhibit T cell-mediated immunity. In this study, PD-L1 mRNA and protein expression was evaluated in canine B cell lymphoma (CLL17-71), large T-cell leukemia (CLGL-90), B cell leukemia (GL-1) and primitive leukocyte round cell neoplasia (CLL-1390). Variable PD-L1 mRNA and protein were observed in these cells with high endogenous expression present in CLL17-71 cells. PD-L1 protein was also observed in canine patient B cell lymphoma tissues using immunostaining. PD-L1 and signal transducer and activator of transcription 1 ( STAT1 ) mRNA expression were reduced in the presence of mitogen-activated protein kinase kinase 1.2 (MEK1/2) inhibitors RDEA119 and AZD6244 in CLL 17-71 cells. RDEA119 had similar effect on PD-L1 and STAT-1 in IFN-γ activated CLL-1390 cells. Overall, these results indicate that PD-L1 is expressed in canine B cell lymphoma. Its inhibition by MEK1/2 inhibitors suggests a possible treatment strategy using targeted drugs which likely could enhance antitumor immune response.
authors.affiliation: Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: S R
authors.initials: SR
authors.lastname: Kumar
authors.affiliation: Veterinary Pathobiology, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: D Y
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: C J
authors.initials: CJ
authors.lastname: Henry
authors.affiliation: Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: J N
authors.initials: JN
authors.lastname: Bryan
authors.affiliation: Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: K L
authors.initials: KL
authors.lastname: Robinson
authors.affiliation: Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
authors.forename: A M
authors.initials: AM
authors.lastname: Eaton
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D005434:Flow Cytometry / Q000662:veterinary; D015151:Immunoblotting / Q000662:veterinary; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000662:veterinary*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; C544830:N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide; D061026:Programmed Cell Death 1 Receptor; D013449:Sulfonamides; D004159:Diphenylamine; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: 
  MEK1
  ; 
  PD-L1
  ; canine; inhibitors; lymphoma