| タイトル |
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ATM-Mediated DNA Damage Signals Mediate Immune Escape through Integrin-αvβ3-Dependent Mechanisms
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| 作成者 |
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Dosaka-Akita, Hirotoshi
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| アクセス権 |
open access |
| 主題 |
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Other
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Integrin-αvβ3
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Other
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Chemoresistance
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DNA damage response
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Antitumor immunity
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Other
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Phagocytosis
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NDC
493
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| 内容注記 |
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Abstract
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Although recent evidences have been unveiling the critical role of tumor microenvironments in tumor progression and metastasis, it remains unclear how resistance to various anticancer modalities is linked with the modulation of tumor microenvironments. We identified a novel mechanism whereby constitutively activated DNA damage signals in anticancer therapy-resistant tumor cells suppress antitumor immunity in an integrin-αvβ3-dependent manner. Integrin-αvβ3 was upregulated on various therapy-resistant tumor cells through chronic activation of ATM/chk2-and NF-κB-mediated pathways. The inhibition of tumor-specific integrin-αvβ3 improved therapeutic efficacies of anticancer drugs by stimulating endogenous host immune systems. As a mechanism of action, tumor-specific integrin-αvβ3 targets dendritic cells to facilitate phagocytosis of live resistant tumor cells, leading to impaired cross-priming of antigen-specific T lymphocytes. Our findings clarified the detrimental effects of DNA damage signals in chemosensitivity and antitumor immunity, and targeting integrin-αvβ3 has a major implication for treating patient refractory to current anticancer regimens.
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| 出版者 |
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American Association for Cancer Research
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| 日付 |
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| 言語 |
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| 資源タイプ |
journal article |
| 出版タイプ |
AM |
| 資源識別子 |
HDL
http://hdl.handle.net/2115/51015
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| 関連 |
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isVersionOf
DOI
https://doi.org/10.1158/0008-5472.CAN-11-2028
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PMID
22094875
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| 収録誌情報 |
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Cancer Research
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巻72
号1
開始ページ56
終了ページ65
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| ファイル |
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| コンテンツ更新日時 |
2023-07-26 |
