ID | 68694 |
フルテキストURL | |
著者 |
Matsuura, Hiroaki
Department of Tumor Microenvironment, Okayama University
Ishino, Takamasa
Department of Tumor Microenvironment, Okayama University
Ninomiya, Toshifumi
Department of Tumor Microenvironment, Okayama University
Ninomiya, Kiichiro
Department of Hematology, Oncology and Respiratory Medicine,Okayama University
Kaken ID
Tachibana, Kota
Department of Dermatology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Honobe-Tabuchi, Akiko
Department of Dermatology, University of Yamanashi
Muto, Yoshinori
Department of Dermatology, University of Yamanashi
Inozume, Takashi
Department of Dermatology, University of Yamanashi
Ueda, Youki
Department of Tumor Microenvironment, Okayama University
Ohashi, Kadoaki
Department of Hematology, Oncology and Respiratory Medicine,Okayama University
ORCID
Kaken ID
researchmap
Maeda, Yoshinobu
Department of Hematology, Oncology and Respiratory Medicine,Okayama University
Kaken ID
researchmap
Nagasaki, Joji
Department of Tumor Microenvironment, Okayama University
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抄録 | Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb.
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キーワード | antigenicity
cancer immunotherapy
CTLA-4
PD-1
regulatory T cell
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発行日 | 2025-02-27
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出版物タイトル |
Cancer Science
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巻 | 116巻
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号 | 5号
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出版者 | Wiley
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開始ページ | 1214
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終了ページ | 1226
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ISSN | 1347-9032
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2025 The Author(s).
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1111/cas.70029
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ライセンス | https://creativecommons.org/licenses/by-nc/4.0/
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Citation | Matsuura, H., Ishino, T., Ninomiya, T., Ninomiya, K., Tachibana, K., Honobe-Tabuchi, A., Muto, Y., Inozume, T., Ueda, Y., Ohashi, K., Maeda, Y., Nagasaki, J. and Togashi, Y. (2025), High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells. Cancer Sci, 116: 1214-1226. https://doi.org/10.1111/cas.70029
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助成機関名 |
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Japan Science and Technology Agency
Canon Foundation
Daiichi Sankyo Foundation of Life Science
MSD Life Science Foundation
Japanese Respiratory Foundation
UBE Foundation
Ryobi Teien Memory Foundation
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助成番号 | JP20H03694
JP21K20859
JP22K15607
JP23ama221324h0001
JPMJFR2049
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