Identification of self-derived molecules that orchestrate tumor microenvironment
Project/Area Number |
18K15179
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49070:Immunology-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Hangai Sho 東京大学, 先端科学技術研究センター, 特任助教 (50785350)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | がん微小環境 / DAMPs / 骨髄由来免疫抑制細胞 / MDSCs / MDSC |
Outline of Final Research Achievements |
We have identified a mechanism by which a novel damage-associated molecular pattern (DAMP), identified by the applicant, regulates the tumor microenvironment (TME) and promotes cancer growth. Through a series of analyses, we found that the novel DAMP induces CXCL1 chemokines via the innate immune receptor Toll-like receptor 2 (TLR2). Furthermore, we found that CXCL1 in turn recruits myeloid-derived suppressor cells, which have potent immunosuppressive activity, to the TME and suppresses the anti-tumor immune response thereby promoting tumor growth.
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Academic Significance and Societal Importance of the Research Achievements |
本研究によりがん細胞より放出される新規DAMPが、TMEを制御しがん増殖を促進するメカニズムの概要が明らかになった。申請者は新規DAMPが、CXCL1/2を誘導し、MDSCを誘導することで抗腫瘍免疫応答を抑制し、がん増殖を促進することを明らかにした。また、ヒト検体の解析により、ヒトにおいても新規DAMPがTME制御によりがん進展を促進している可能性が示唆された。本研究は近年進展が著しい、自己由来分子によるTME制御メカニズムに新たな視点を提供したものと考えられる。今後、新規DAMP中和抗体の抗腫瘍効果の検討を進めることで、新規DAMPの治療標的としての役割が明らかになることが期待される
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] HMGB1-mediated chromatin remodeling attenuates Il24 gene expression for the protection from allergic contact dermatitis2021
Author(s)
Senda N, Yanai H, Hibino S, Li L, Mizushima Y, Miyagaki T, Saeki M, Kishi Y, Hangai S, Nishio J, Sugaya M, Taniguchi T, Sato S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 118
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis.2019
Author(s)
Negishi H, Endo N, Nakajima Y, Nishiyama T, Tabunoki Y, Nishio J, Koshiba R, Matsuda A, Matsuki K, Okamura T, Negishi-Koga T, Ichinohe T, Takemura S, Ishiwata H, Iemura SI, Natsume T, Abe T, Kiyonari H, Doi T, Hangai S, Yanai H, Fujio K, Yamamoto K, Taniguchi T.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 116
Issue: 47
Pages: 23653-23661
DOI
Related Report
Peer Reviewed / Open Access
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