Journal Article

Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

Kato, Yukinari, Ohashi, Kazuhiko, Nishimori, Asami, Ikebuchi, Ryoyo, Okagawa, Tomohiro, Izumi, Yusuke, Murata, Shiro, Kagawa, Yumiko, Takagi, Satoshi, Suzuki, Yasuhiko, Maekawa, Naoya, Nakajima, Chie, Konnai, Satoru

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma / Animals / Antibodies / Apoptosis / B7-H1 Antigen - biosynthesis / Biocompatibility / Biology and Life Sciences / Biomedical materials / Bone cancer / Breast cancer / Cancer / Cancer immunotherapy / Chemical compounds / Clinical trials / Cytotoxicity / Development and progression / Diagnosis / Disease control / Diseases and pests / Dog Diseases - metabolism / Dog Diseases - pathology / Dogs / Female / Gene expression / Gene Expression Regulation, Neoplastic / Genetic aspects / Immunoglobulins / Immunohistochemistry / Immunosuppression / Immunotherapy / Kidney cancer / Ligands / Lung carcinoma / Lymphocytes / Lymphocytes - metabolism / Lymphocytes - pathology / Lymphocytes T / Male / Medical prognosis / Medical research / Medicine and Health Sciences / Melanoma / Melanoma - metabolism / Melanoma - pathology / Melanoma - veterinary / Mouth Neoplasms - metabolism / Mouth Neoplasms - pathology / Mouth Neoplasms - veterinary / Neoplasm Proteins - biosynthesis / Non-small cell lung carcinoma / Osteosarcoma / PD-1 protein / PD-L1 protein / Pharmacology / Physiological aspects / Programmed Cell Death 1 Receptor - biosynthesis / Prostate / Prostate cancer / Regression analysis / Renal cell carcinoma / Research and Analysis Methods / Sarcoma / Small cell lung carcinoma / T cell receptors / T-cell receptor / Teaching hospitals / Therapeutic applications / Tumor-infiltrating lymphocytes / Tumors / Veterinary colleges / Veterinary medicine / Zoonoses