title: Immune regulation of canine tumour and macrophage PD-L1 expression.
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.
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: G
authors: G
authors: Hartley
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: E
authors: E
authors: Faulhaber
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: A
authors: A
authors: Caldwell
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: J
authors: J
authors: Coy
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: J
authors: J
authors: Kurihara
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: A
authors: A
authors: Guth
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: D
authors: D
authors: Regan
authors: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Ft. Collins, CO, USA.
authors: S
authors: S
authors: Dow
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism; D004285:Dogs; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*
chemical_list: D060890:B7-H1 Antigen; D007371:Interferon-gamma
keywords: cancer; checkpoint molecule; dog; immune