title: Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
abstract: Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Maekawa
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okagawa
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan; North Lab, Sapporo, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Nakajima
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D019556:COS Cells; D002522:Chlorocebus aethiops; D004285:Dogs; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma