2024-03-29T05:59:58Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/893352023-05-25T07:32:02Zhdl_2115_20048hdl_2115_140Regulation of programmed death ligand 1 expression by interferon-gamma and tumour necrosis factor-alpha in canine tumour cell linesOwaki, Ryo1000010849962Deguchi, Tatsuya1000040396304Konnai, Satoru1000070829035Maekawa, Naoya1000080829036Okagawa, Tomohiro1000050566156Hosoya, KenjiKim, Sangho1000090649112Sunaga, TakafumiOkumura, Masahirometadata only accesscell signallingimmunologyin vitro modelsoncologysmall animal649Expression of programmed death ligand 1 (PD-L1) on tumour cells provides an immune evasion mechanism by inducing suppression of cytotoxic T cells. Various regulatory mechanisms of PD-L1 expression have been described in human tumours, however, little is known in canine tumours. To investigate whether inflammatory signalling is involved in PD-L1 regulation in canine tumours, the effects of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha treatment were examined in canine malignant melanoma cell lines (CMeC and LMeC) and an osteosarcoma cell line (HMPOS). The protein level of PD-L1 expression was upregulated by IFN-gamma and TNF-alpha stimulation. Upon IFN-gamma stimulation, all cell lines showed an increase in expression of PD-L1, signal transducer and activator of transcription (STAT)1, STAT3 and genes regulated by STAT activation. Upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib. Contrastingly, upon TNF-alpha stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF-kappa B) gene RELA and genes regulated by NF-kappa B activation, whereas expression of PD-L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF-kappa B inhibitor, BAY 11-7082. The expression level of cell surface PD-L1 induced by IFN-gamma and TNF-alpha treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-gamma and TNF-alpha stimulation is regulated via the JAK-STAT and NF-kappa B signalling pathways, respectively. These results provide insights into the role of inflammatory signalling in PD-L1 regulation in canine tumours.John Wiley & Sons2023-05-25engjournal articleNAhttp://hdl.handle.net/2115/89335https://doi.org/10.1111/vco.128861476-5810Veterinary and comparative oncology