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Programmed death ligand 1 is expressed in canine B cell lymphoma and downregulated by MEK inhibitors
Author(s) -
Kumar S. R.,
Kim D. Y.,
Henry C. J.,
Bryan J. N.,
Robinson K. L.,
Eaton A. M.
Publication year - 2017
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12297
Subject(s) - cancer research , stat protein , lymphoma , canine lymphoma , microbiology and biotechnology , stat1 , protein kinase a , b cell , leukemia , t cell , antigen , activator (genetics) , biology , immune system , chemistry , signal transduction , kinase , antibody , immunology , receptor , stat3 , biochemistry
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.