Oral Presentation International Veterinary Immunology Symposium 2016

Expression of canine immune checkpoint molecules PD-1/PD-L1 and the therapeutic potential of anti-PD-L1 antibody in canine malignant cancers (#71)

Naoya Maekawa 1 , Satoru Konnai 1 , Tomohiro Okagawa 1 , Asami Nishimori 1 , Ryoyo Ikebuchi 1 , Satoshi Takagi 2 , Yumiko Kagawa 3 4 , Shiro Murata 1 , Kazuhiko Ohashi 1
  1. Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
  2. Veterinary Teaching Hospital, Hokkaido University, Sapporo, Japan
  3. Department of Diagnostic Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
  4. North Lab, Sapporo, Japan

  Programmed death-1 (PD-1) is a receptor with immunosuppressive function, and is upregulated on lymphocytes upon persistent antigen stimulation. A ligand for PD-1, PD-Ligand 1 (PD-L1), is expressed in various types of cancer cells, indicating that the PD-1/PD-L1 axis is a common mechanism for immune evasion of cancers. Interestingly, the blockade of this pathway enhances anti-tumor immune responses in humans and mice. Thus, immune checkpoint inhibitors, such as anti-PD-1 or PD-L1 antibodies, have been used for the treatment of human cancer, and considered promising immunotherapy for several types of malignancies. However, there are few reports on the involvement of the PD-1/PD-L1 pathway in anti-cancer immunity of dogs.

  Molecular characterization and expression analysis of canine PD-1/PD-L1 were performed in order to determine whether this strategy can be applied to the treatment of canine cancers. Recombinant canine PD-1 was shown to bind to PD-L1-expressing cells, and its binding was blocked by an anti-PD-L1 antibody. Immunohistochemical analysis revealed that canine oral melanoma (36/40), osteosarcoma (7/10), hemangiosarcoma (6/10), mast cell tumor (3/5) and some other cancers express PD-L1, and higher PD-1 expression on tumor-infiltrating lymphocytes was observed in oral melanoma samples (n = 6, p < 0.05), determined by flow cytometer. Importantly, the treatment with an anti-PD-L1 antibody enhanced the production of interferon-gamma from tumor-infiltrating cells, suggesting a possible application of PD-1/PD-L1 inhibitors for the treatment of canine cancers. Therefore, therapeutic effect of anti-PD-L1 antibody should be further investigated in vivo.