title: PD-1 expression by canine T cells and functional effects of PD-1 blockade.
abstract: The co-inhibitory checkpoint molecule programmed death receptor 1 (PD-1) can trigger T cell functional exhaustion upon binding to its ligand PD-L1 expressed on tumour cells or macrophages. PD-1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD-1 were assessed for T cell binding and induction of functional activation. A total of 5-10% of CD4 T cells and 20-25% of CD8 T cells from healthy dogs expressed PD-1, and PD-1 expression was upregulated on T cells from dogs with cancer. Functionally, PD-1 antibodies significantly enhanced T-cell activation, as assessed by proliferation and interferon-gamma (IFN-γ) production. PD-1 antibodies also reversed T-cell suppression induced by canine soluble PD-L1 and by tumour cells and tumour explant fragments. These findings indicate that PD-1 antibodies have potential for use in cancer immunotherapy in dogs.
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO, USA.
authors.forename: J
authors.initials: J
authors.lastname: Coy
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Caldwell
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chow
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Guth
authors.affiliation: Flint Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Ft. Collins, CO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dow
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D007371:Interferon-gamma / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
keywords: T cell; cytokine; immune; tumour