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ID 68694
フルテキストURL
fulltext.pdf 4.66 MB
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
Togashi, Yosuke Department of Tumor Microenvironment, Okayama University ORCID Kaken ID researchmap
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.
キーワード
antigenicity
cancer immunotherapy
CTLA-4
PD-1
regulatory T cell
発行日
2025-02-27
出版物タイトル
Cancer Science
116巻
5号
出版者
Wiley
開始ページ
1214
終了ページ
1226
ISSN
1347-9032
資料タイプ
学術雑誌論文
言語
英語
OAI-PMH Set
岡山大学
著作権者
© 2025 The Author(s).
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1111/cas.70029
ライセンス
https://creativecommons.org/licenses/by-nc/4.0/
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
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
助成番号
JP20H03694
JP21K20859
JP22K15607
JP23ama221324h0001
JPMJFR2049