azd-6244 and Lymphoma--B-Cell

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.

Topics: Animals; Benzimidazoles; Cell Line, Tumor; Diphenylamine; Dog Diseases; Dogs; Down-Regulation; Flow Cytometry; Immunoblotting; Lymphoma, B-Cell; Mitogen-Activated Protein Kinase Kinases; Polymerase Chain Reaction; Programmed Cell Death 1 Receptor; Sulfonamides