Immune-mediated antitumor effect by type 2 diabetes drug, metformin
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- Shingo Eikawa
- Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; and
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- Mikako Nishida
- Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; and
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- Shusaku Mizukami
- Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; and
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- Chihiro Yamazaki
- Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; and
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- Eiichi Nakayama
- Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Okayama 701-0193, Japan
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- Heiichiro Udono
- Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; and
Description
<jats:title>Significance</jats:title> <jats:p> The multifunctional ability of CTLs is downregulated by interaction between immune-checkpoint molecules expressed on CTLs and their ligands expressed on cancer cells, referred to as immune exhaustion. The antibody-mediated, immune-checkpoint blockade turned out to a promising method for immunotherapy against advanced melanoma. Metformin, a drug prescribed for patients with type 2 diabetes, has been recognized to have anti-cancer effect. We found that CD8 <jats:sup>+</jats:sup> tumor infiltrating lymphocytes (TILs) is a target of metformin. CD8 <jats:sup>+</jats:sup> TILs inevitably undergo immune exhaustion, characterized by diminished production of multiple cytokines such as IL-2, TNFα, and IFNγ, followed by elimination with apoptosis. Metformin is able to counter the state. Along with conventional therapy, treatment of cancer patients with metformin may have a great advantage for cancer therapy. </jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (6), 1809-1814, 2015-01-26
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1360283692110097152
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref
- KAKEN