Molecular machineries of antitumor immune responses triggered by anticancer chemotherapy
| Project/Area Number |
23501283
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor immunology
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| Research Institution | Hokkaido University |
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Principal Investigator |
JINUSHI Masahisa 北海道大学, 遺伝子病制御研究所, 准教授 (40318085)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIYAMA Hironori 北海道大学, 遺伝子病制御研究所, 准教授 (10253147)
千葉 殖幹 愛知県がんセンター(研究所), その他部局等, その他 (20550023)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 癌 / 免疫 / 腫瘍ミエロイド細胞 / TIM-3 / TIM-4 / HMGB1 / オートファジー / 抗がん剤 / 腫瘍免疫 / ミエロイド細胞 / 抗がん剤耐性 / 樹状細胞 / 核酸 / エンドゾーム / 国際情報交換 / 抗癌剤 / MFG-E8 / ネクローシス / RIP1 / RIP3 |
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| Outline of Final Research Achievements |
Anticancer agents modulate host immune responses through various regulatory mechanisms. By screening the critical factors that increase upon anticancer therapies and regulate the immune responses by tumor-associated myeloid cells (TAM), ｗe identified several key factors expressed on TAM, which greatly influence antitumor effects of chemotherapy. For example, TIM-3 interacts with HMGB1 released from chemotherapy-treated tumor cells, and suppresses innate pattern recognition signals mediated by nucleic acids. On the other hands, DAMP released from chemotherapy-damaged tumors induced TIM-4 on TAM. TIM-4 promotes the autophagy-mediated lysosomal degradation of ingested tumors and represses antigen presentation and tumor-specific CTL responses.Our findings provide new evidences that targeting of TAM-derived factors provides new strategy to improve the therapeutic responses to anticancer regiments and eradicate therapy-resistant tumors.
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads to reduced antigen presentation and increased immune tolerance.2013
Author(s)
Baghdadi M, Yoneda A, Yamashina T, Nagao H, Komohara Y, Nagai S, Akiba H, Foretz M, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Takeya M, Viollet B, Yagita H, Jinushi M
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Journal Title
Immunity
Volume: 39
Issue: 6
Pages: 1070-1081
DOI
Related Report
Peer Reviewed
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[Journal Article] Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. S.2012
Author(s)
Chiba, M. Baghdadi, H. Akiba, H. Yoshiyama, I. Kinoshita, H. Dosaka-Akita, Y. Fujioka, Y. Ohba, J. V. Gorman, J. D. Colgan, M. Hirashima, T. Uede, A. Takaoka, H. Yagita and M. Jinushi.
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Journal Title
Nat. Immunol.
Volume: 13
Issue: 9
Pages: 832-842
DOI
Related Report
Peer Reviewed
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