| 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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