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

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, l...

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Autores principales: Maekawa, Naoya, Konnai, Satoru, Asano, Yumie, Otsuka, Takumi, Aoki, Eri, Takeuchi, Hiroto, Kato, Yukinari, Kaneko, Mika K., Yamada, Shinji, Kagawa, Yumiko, Nishimura, Maki, Takagi, Satoshi, Deguchi, Tatsuya, Ohta, Hiroshi, Nakagawa, Takayuki, Suzuki, Yasuhiko, Okagawa, Tomohiro, Murata, Shiro, Ohashi, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879432/
https://www.ncbi.nlm.nih.gov/pubmed/36701405
http://dx.doi.org/10.1371/journal.pone.0281143
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author Maekawa, Naoya
Konnai, Satoru
Asano, Yumie
Otsuka, Takumi
Aoki, Eri
Takeuchi, Hiroto
Kato, Yukinari
Kaneko, Mika K.
Yamada, Shinji
Kagawa, Yumiko
Nishimura, Maki
Takagi, Satoshi
Deguchi, Tatsuya
Ohta, Hiroshi
Nakagawa, Takayuki
Suzuki, Yasuhiko
Okagawa, Tomohiro
Murata, Shiro
Ohashi, Kazuhiko
author_facet Maekawa, Naoya
Konnai, Satoru
Asano, Yumie
Otsuka, Takumi
Aoki, Eri
Takeuchi, Hiroto
Kato, Yukinari
Kaneko, Mika K.
Yamada, Shinji
Kagawa, Yumiko
Nishimura, Maki
Takagi, Satoshi
Deguchi, Tatsuya
Ohta, Hiroshi
Nakagawa, Takayuki
Suzuki, Yasuhiko
Okagawa, Tomohiro
Murata, Shiro
Ohashi, Kazuhiko
author_sort Maekawa, Naoya
collection PubMed
description 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-γ 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.
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spelling pubmed-98794322023-01-27 Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors Maekawa, Naoya Konnai, Satoru Asano, Yumie Otsuka, Takumi Aoki, Eri Takeuchi, Hiroto Kato, Yukinari Kaneko, Mika K. Yamada, Shinji Kagawa, Yumiko Nishimura, Maki Takagi, Satoshi Deguchi, Tatsuya Ohta, Hiroshi Nakagawa, Takayuki Suzuki, Yasuhiko Okagawa, Tomohiro Murata, Shiro Ohashi, Kazuhiko PLoS One Research Article 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-γ 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. Public Library of Science 2023-01-26 /pmc/articles/PMC9879432/ /pubmed/36701405 http://dx.doi.org/10.1371/journal.pone.0281143 Text en © 2023 Maekawa et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Maekawa, Naoya
Konnai, Satoru
Asano, Yumie
Otsuka, Takumi
Aoki, Eri
Takeuchi, Hiroto
Kato, Yukinari
Kaneko, Mika K.
Yamada, Shinji
Kagawa, Yumiko
Nishimura, Maki
Takagi, Satoshi
Deguchi, Tatsuya
Ohta, Hiroshi
Nakagawa, Takayuki
Suzuki, Yasuhiko
Okagawa, Tomohiro
Murata, Shiro
Ohashi, Kazuhiko
Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title_full Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title_fullStr Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title_full_unstemmed Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title_short Molecular characterization of feline immune checkpoint molecules and establishment of PD-L1 immunohistochemistry for feline tumors
title_sort molecular characterization of feline immune checkpoint molecules and establishment of pd-l1 immunohistochemistry for feline tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879432/
https://www.ncbi.nlm.nih.gov/pubmed/36701405
http://dx.doi.org/10.1371/journal.pone.0281143
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