Regulation of programmed death ligand 1 expression by interferon-γ and tumour necrosis factor-α in canine tumour cell lines

by Selleckchem | Apr 12 2023

Expression 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)-γ and tumour necrosis factor (TNF)-α 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-γ and TNF-α stimulation. Upon IFN-γ 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-α stimulation, all cell lines exhibited higher gene expression of the nuclear factor kappa B (NF-κB) gene RELA and genes regulated by NF-κB activation, whereas expression of PD-L1 was upregulated in LMeC only. Upregulated expression of these genes was suppressed by the addition of an NF-κB inhibitor, BAY 11-7082. The expression level of cell surface PD-L1 induced by IFN-γ and TNF-α treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-γ and TNF-α stimulation is regulated via the JAK-STAT and NF-κB signalling pathways, respectively. These results provide insights into the role of inflammatory signalling in PD-L1 regulation in canine tumours.

Comments：

The study investigated the regulatory mechanisms of PD-L1 expression in canine tumours by examining the effects of IFN-γ and TNF-α treatment in canine malignant melanoma and osteosarcoma cell lines. The findings suggest that inflammatory signaling pathways, specifically JAK-STAT and NF-κB, are involved in the upregulation of PD-L1 expression in these cell lines.

Upon IFN-γ stimulation, all cell lines showed an increase in expression of PD-L1, as well as signal transducer and activator of transcription (STAT)1, STAT3, and genes regulated by STAT activation. The upregulated expression of these genes was suppressed by the addition of a JAK inhibitor, oclacitinib.

On the other hand, upon TNF-α stimulation, all cell lines exhibited higher gene expression of the NF-κB gene RELA and genes regulated by NF-κB activation, while PD-L1 expression was upregulated in LMeC only. The upregulated expression of these genes was suppressed by the addition of an NF-κB inhibitor, BAY 11-7082.

The expression level of cell surface PD-L1 induced by IFN-γ and TNF-α treatment was reduced by oclacitinib and BAY 11-7082, respectively, indicating that upregulation of PD-L1 expression by IFN-γ and TNF-α stimulation is regulated via the JAK-STAT and NF-κB signaling pathways, respectively.

Overall, the study provides insights into the role of inflammatory signaling in the regulation of PD-L1 expression in canine tumours and suggests that targeting these pathways may be a potential therapeutic strategy for treating canine cancers.