Immune regulation of canine tumour and macrophage PD-L1 expression.
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| Abstract |
Expression of programmed cell death receptor ligand 1 (PD-L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD-L1 expression by tumor cells and tumor-infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD-L1 expression and for responsiveness to immune stimuli. We found that PD-L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD-L1 expression by all tumor cell lines was observed following IFN-γ exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte-derived macrophages did not express PD-L1 constitutively, but did significantly upregulate expression following treatment with IFN-γ. These findings suggest that most canine tumors express PD-L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD-L1 expression. Therefore the upregulation of PD-L1 expression by tumor cells and by tumor-infiltrating macrophages in response to cytokines such as IFN-γ may represent an important mechanism of tumor-mediated T-cell suppression in dogs as well as in humans.
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| Authors | G Hartley, E Faulhaber, A Caldwell, J Coy, J Kurihara, A Guth, D Regan, S Dow |
| Journal | Veterinary and comparative oncology (Vet Comp Oncol) Vol. 15 Issue 2 Pg. 534-549 (Jun 2017) ISSN: 1476-5829 [Electronic] England |
| PMID | 26842912 (Publication Type: Journal Article) |
| Copyright | © 2016 John Wiley & Sons Ltd. |
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