Kumar S R, Kim D Y, Henry C J, Bryan J N, Robinson K L, Eaton A M
Comparative Oncology, Radiopharmaceutical and Epigenetics Laboratory, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
Veterinary Pathobiology, School of Veterinary Medicine, University of Missouri, Columbia, Missouri.
Vet Comp Oncol. 2017 Dec;15(4):1527-1536. doi: 10.1111/vco.12297. Epub 2017 Jan 22.
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.
程序性死亡配体1(PD-L1)在抗原呈递细胞和肿瘤中的表达可抑制T细胞介导的免疫反应。在本研究中,对犬B细胞淋巴瘤(CLL17-71)、大T细胞白血病(CLGL-90)、B细胞白血病(GL-1)和原始白细胞圆形细胞瘤(CLL-1390)中的PD-L1 mRNA和蛋白表达进行了评估。在这些细胞中观察到了可变的PD-L1 mRNA和蛋白,其中CLL17-71细胞中存在高内源性表达。使用免疫染色在犬患者B细胞淋巴瘤组织中也观察到了PD-L1蛋白。在有丝分裂原活化蛋白激酶激酶1.2(MEK1/2)抑制剂RDEA119和AZD6244存在的情况下,CLL 17-71细胞中PD-L1和信号转导及转录激活因子1(STAT1)的mRNA表达降低。RDEA119对IFN-γ激活的CLL-1390细胞中的PD-L1和STAT-1有类似作用。总体而言,这些结果表明PD-L1在犬B细胞淋巴瘤中表达。MEK1/2抑制剂对其的抑制作用提示了一种可能的治疗策略,即使用靶向药物,这可能会增强抗肿瘤免疫反应。