ID | 63200 |
フルテキストURL | |
著者 |
Nagasaki, Joji
Chiba Cancer Center, Research Institute
Inozume, Takashi
Chiba Cancer Center, Research Institute
Sax, Nicolas
KOTAI Biotechnologies, Inc.
Ariyasu, Ryo
Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
Ishikawa, Masakazu
KOTAI Biotechnologies, Inc.
Yamashita, Kazuo
KOTAI Biotechnologies, Inc.
Kawazu, Masahito
Division of Cellular Signaling, National Cancer Center, Research Institute
Ueno, Toshihide
Division of Cellular Signaling, National Cancer Center, Research Institute
Irie, Takuma
Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
Tanji, Etsuko
Chiba Cancer Center, Research Institute
Morinaga, Takao
Chiba Cancer Center, Research Institute
Honobe, Akiko
Department of Dermatology, University of Yamanashi
Ohnuma, Takehiro
Department of Dermatology, University of Yamanashi
Yoshino, Mitsuru
Department of Thoracic Surgery, Chiba Cancer Center
Iwata, Takekazu
Department of Thoracic Surgery, Chiba Cancer Center
Kawase, Katsushige
Chiba Cancer Center, Research Institute
Sasaki, Keita
Department of Head and Neck Surgery, Chiba Cancer Center
Hanazawa, Toyoyuki
Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine
Kochin, Vitaly
Department of Immunology, Nagoya University Graduate School of Medicine
Kawamura, Tatsuyoshi
Department of Dermatology, University of Yamanashi
Matsue, Hiroyuki
Department of Dermatology, Chiba University Graduate School of Medicine
Hino, Masayuki
Department of Hematology, Graduate School of Medicine, Osaka City University
Mano, Hiroyuki
Division of Cellular Signaling, National Cancer Center, Research Institute
Suzuki, Yutaka
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
Nishikawa, Hiroyoshi
Division of Cancer Immunology, National Cancer Center, Research Institute, Exploratory Oncology Research and Clinical Trial Center (EPOC)
Togashi, Yosuke
Department of Tumor Microenvironment, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs.
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発行日 | 2022-02-01
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出版物タイトル |
Cell Reports
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巻 | 38巻
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号 | 5号
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出版者 | Cell Press
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開始ページ | 110331
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ISSN | 2211-1247
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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 | © 2022 The Author(s).
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論文のバージョン | publisher
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PubMed ID | |
NAID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1016/j.celrep.2022.110331
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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