ID | 118888 |
著者 |
Afroj, Tania
Tokushima University
Nguyen, Na Thi
Tokushima University
米田, 浩人
Tokushima University
大塚, 憲司
Tokushima University
Sugimoto, Masamichi
Chugai Pharmaceutical
Kondoh, Osamu
Chugai Pharmaceutical
軒原, 浩
Tokushima University
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資料タイプ |
学術雑誌論文
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抄録 | Recent clinical trials revealed that immune checkpoint inhibitors and antiangiogenic reagent combination therapy improved the prognosis of various cancers. We investigated the roles of fibrocytes, collagen-producing monocyte-derived cells, in combination immunotherapy. Anti-VEGF (vascular endothelial growth factor) antibody increases tumor-infiltrating fibrocytes and enhances the antitumor effects of anti-PD-L1 (programmed death ligand 1) antibody in vivo. Single-cell RNA sequencing of tumor-infiltrating CD45+ cells identifies a distinct “fibrocyte cluster” from “macrophage clusters” in vivo and in lung adenocarcinoma patients. A sub-clustering analysis reveals a fibrocyte sub-cluster that highly expresses co-stimulatory molecules. CD8+ T cell-costimulatory activity of tumor-infiltrating CD45+CD34+ fibrocytes is enhanced by anti-PD-L1 antibody. Peritumoral implantation of fibrocytes enhances the antitumor effect of PD-L1 blockade in vivo; CD86−/− fibrocytes do not. Tumor-infiltrating fibrocytes acquire myofibroblast-like phenotypes through transforming growth factor β (TGF-β)/small mothers against decapentaplegic (SMAD) signaling. Thus, TGF-βR/SMAD inhibitor enhances the antitumor effects of dual VEGF and PD-L1 blockade by regulating fibrocyte differentiation. Fibrocytes are highlighted as regulators of the response to programmed death 1 (PD-1)/PD-L1 blockade.
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掲載誌名 |
Cell Reports
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ISSN | 22111247
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出版者 | Elsevier
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巻 | 42
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号 | 3
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開始ページ | 112162
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発行日 | 2023-03-03
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権利情報 | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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出版社版DOI | |
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フルテキストファイル | |
言語 |
eng
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著者版フラグ |
出版社版
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部局 |
医学系
病院
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