Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma.
Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs.
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Naoya
N
Maekawa
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Satoru
S
Konnai
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Tomohiro
T
Okagawa
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Asami
A
Nishimori
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ryoyo
R
Ikebuchi
Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Yusuke
Y
Izumi
Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Satoshi
S
Takagi
North Lab, Sapporo, Japan.|Department of Diagnostic Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Yumiko
Y
Kagawa
Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Chie
C
Nakajima
Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Yasuhiko
Y
Suzuki
Department of Regional Innovation, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Yukinari
Y
Kato
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Shiro
S
Murata
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kazuhiko
K
Ohashi
D000818:Animals; D060890:B7-H1 Antigen / Q000096:biosynthesis; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*
D060890:B7-H1 Antigen; D009363:Neoplasm Proteins; D061026:Programmed Cell Death 1 Receptor