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Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties
https://repo.qst.go.jp/records/79070
https://repo.qst.go.jp/records/790703689885f-f7e1-4a14-a623-3f587b9703ca
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-02-26 | |||||
| タイトル | ||||||
| タイトル | Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Terashima, Yuya
× Terashima, Yuya× Toda, Etsuko× Itakura, Meiji× Otsuji, Mikiya× H.W. Shand, Francis× Okumura, Kazuhiro× Yoshinaga, Sosuke× Komohara, Yoshihiro× Takeda, Mitsuhiro× Kokubo, Kana× Meing-Chen, Chen× Yokoi, Sana× Rokutan, Hirofumi× Kofuku, Yutaka× Ohnishi, Koji× Ohira, Miki× Iizasa, Toshihiko× Nakano, Hirofumi× Okabe, Takayoshi× Kojima, Hirotatsu× Shimizu, Akira× Kanegasaki, Shiro× Ming-Rong, Zhang× Shimada, Ichio× Nagase, Hiroki× Terasawa, Hiroaki× Mastushima, Kouji× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Tumor-associated macrophages affect tumor progression and resistance to immune checkpoint therapy. Here, we identify the chemokine signal regulator FROUNT as a target to control tumor-associated macrophages. The low level FROUNT expression in patients with cancer correlates with better clinical outcomes. Frount-deficiency markedly reduces tumor progression and decreases macrophage tumor-promoting activity. FROUNT is highly expressed in macrophages, and its myeloid-specific deletion impairs tumor growth. Further, the anti-alcoholism drug disulfiram (DSF) acts as a potent inhibitor of FROUNT. DSF interferes with FROUNT-chemokine receptor interactions via direct binding to a specific site of the chemokine receptor-binding domain of FROUNT, leading to inhibition of macrophage responses. DSF monotherapy reduces tumor progression and decreases macrophage tumor-promoting activity, as seen in the case of Frount-deficiency. Moreover, co-treatment with DSF and an immune checkpoint antibody synergistically inhibits tumor growth. Thus, inhibition of FROUNT by DSF represents a promising strategy for macrophage-targeted cancer therapy. | |||||
| 書誌情報 |
Nature Communications 巻 11, p. 609, 発行日 2020-02 |
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| 出版者 | ||||||
| 出版者 | SPRINGER NATURE | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2041-1723 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1038/s41467-020-14338-5 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.nature.com/articles/s41467-020-14338-5 | |||||
