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Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors

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Title: Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
Authors: Maekawa, Naoya Browse this author →KAKEN DB
Konnai, Satoru Browse this author →KAKEN DB
Asano, Yumie Browse this author
Otsuka, Takumi Browse this author
Aoki, Eri Browse this author
Takeuchi, Hiroto Browse this author
Kato, Yukinari Browse this author
Kaneko, Mika K. Browse this author
Yamada, Shinji Browse this author
Kagawa, Yumiko Browse this author
Nishimura, Maki Browse this author
Takagi, Satoshi Browse this author
Deguchi, Tatsuya Browse this author
Ohta, Hiroshi Browse this author
Nakagawa, Takayuki Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Okagawa, Tomohiro Browse this author →KAKEN DB
Murata, Shiro Browse this author →KAKEN DB
Ohashi, Kazuhiko Browse this author →KAKEN DB
Issue Date: 26-Jan-2023
Publisher: PLOS
Journal Title: PLoS ONE
Volume: 18
Issue: 1
Start Page: e0281143
Publisher DOI: 10.1371/journal.pone.0281143
Abstract: Spontaneous tumors are a major cause of death in cats. Treatment of human tumors has progressed dramatically in the past decade, partly due to the success of immunotherapies using immune checkpoint inhibitors, such as anti-programmed death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) antibodies. However, little is known about the PD-1 pathway and its association with tumor disease in cats. This study investigated the applicability of anti-PD-1/PD-L1 therapy in feline tumors. We first determined the complete coding sequence of feline PD-L1 and PD-L2, and found that the deduced amino acid sequences of feline PD-L1/PD-L2 share high sequence identities (66-83%) with orthologs in other mammalian species. We prepared recombinant feline PD-1, PD-L1, and PD-L2 proteins and confirmed receptor-ligand binding between PD-1 and PD-L1/PD-L2 using flow cytometry. Next, we established an anti-feline PD-L1 monoclonal antibody (clone CL1Mab-7) to analyze the expression of PD-L1. Flow cytometry using CL1Mab-7 revealed the cell surface expression of PD-L1 in a feline macrophage (Fcwf-4) and five mammary adenocarcinoma cell lines (FKNp, FMCm, FYMp, FONp, and FONm), and showed that PD-L1 expression was upregulated by interferon-gamma stimulation. Finally, immunohistochemistry using CL1Mab-7 also showed PD-L1 expression in feline squamous cell carcinoma (5/5, 100%), mammary adenocarcinoma (4/5, 80%), fibrosarcoma (5/5, 100%), and renal cell carcinoma (2/2, 100%) tissues. Our results strongly encourage further investigations of the PD-1/PD-L1 pathway as a potential therapeutic target for feline tumors.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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