Elucidation of mechanism for liver metastasis of colon cancer through IL-6-mediated immunosuppression and its application to development of novel cancer therapy
Project/Area Number |
16K10526
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Hokkaido University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
武冨 紹信 北海道大学, 医学研究院, 教授 (70363364)
川村 秀樹 北海道大学, 医学研究院, 客員研究員 (70645960)
崎浜 秀康 北海道大学, 医学研究院, 客員研究員 (50533676)
本間 重紀 北海道大学, 医学研究院, 講師 (30533674)
下國 達志 北海道大学, 医学研究院, 客員研究員 (30596458)
吉田 雅 北海道大学, 大学病院, 特任助教 (70772333)
北村 秀光 北海道大学, 遺伝子病制御研究所, 准教授 (40360531)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 大腸がん / 肝転移 / IL-6 / 樹状細胞 / キラーT細胞 / microRNA / がん免疫治療 / PD-L1 / 免疫チエックポイント阻害治療 / STAT3 / マクロファージ / 小腸大腸肛門外科 |
Outline of Final Research Achievements |
In this study, we established a liver metastasis mouse model and investigated the effect of IL-6 produced from tumor-bearing host on the tumorigenesis in the liver. We found that liver metastasis of colon cancer cells was significantly reduced in IL-6-deficient mice compared to wild-type mice. Depletion of dendritic cells and macrophages or killer T cells from the liver metastasis model mice cancelled the reduction of liver metastasis under IL-6-deficient condition. We identified IL-6-related microRNA by using serum of colorectal cancer patients and confirmed that liver metastasis and serum IL-6 levels of immunodeficient mice were augment by the IL-6-related microRNA-overexpressing human colon cancer cells compared to the mock control cells. Based on these findings we speculate that blockade of IL-6 signaling may be a promising strategy in the development of effective cancer immunotherapy for cancer patients.
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Academic Significance and Societal Importance of the Research Achievements |
日本人の死亡原因の第一位はがんで、特に大腸がんは年々増加をしており、既存の標準治療に加え、新たな治療の開発が望まれている。生体にはがん免疫監視機構が存在し、がん細胞を特異的に排除する能力が備わっており、その能力を賦活する、がん特異的免疫応答の活性化によるがん免疫治療は、副作用の少ないがん治療法として着目されている。本研究の成果は、IL-6シグナルの下流標的分子ががん特異的免疫応答を強化する可能性を示唆しており、がん免疫治療のさらなる進化と、既存の化学療法との併用等の新展開が期待され、学術的にも社会的にも意義深いものである。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Lack of IL-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy.2017
Author(s)
Ohno Y, Toyoshima Y, Yurino H, Monma N, Xiang H, Sumida K, Kaneumi S, Terada S, Hashimoto S, Ikeo K, Homma S, Kawamura H, Takahashi N, Taketomi A, Kitamura H
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Journal Title
Cancer Science
Volume: 108
Issue: 10
Pages: 1959-1966
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Lack of IL-6 in tumor microenvironment augments type-1 anti-tumor immune responses and facilitates efficacy of cancer immunotherapy2018
Author(s)
Yosuke Ohno, Hidemitsu Kitamura, Yujiro Toyoshima, Huihui Xiang, Sumida Kentaro, Kaneumi Shun, Kazuho Ikeo, Shinichi Hashimoto, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi
Organizer
第77回 日本癌学会学術総会 (受賞講演)
Related Report
Invited
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[Presentation] IL-6 suppresses dendritic cell-mediated antitumor immunity and promotes liver metastasis of colorectal cancer cells2017
Author(s)
Yujiro Toyoshima, Huihui Xiang, Satoshi Terada, Naoki Okada, Shuhei Kii, Yosuke Ohno, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Organizer
The 36th Sapporo International Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] IL-6 attenuates function of dendritic cells and effector T cells in tumor-bearing host2017
Author(s)
Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Huihui Xiang, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi
Organizer
The 36th Sapporo International Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] IL-6 suppresses dendritic cell-mediated antitumor immunity and promotes liver metastasis of colorectal cancer cells2017
Author(s)
Yujiro Toyoshima , Huihui Xiang, Satoshi Terada, Naoki Okada, Shuhei Kii, Yosuke Ohno, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Organizer
第76回 日本癌学会学術総会 (一般演題)
Related Report
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[Presentation] IL-6 causes dysfunction of antitumor immunity and promotes tumorigenesis in a liver metastasis model using colorectal cancer cells2016
Author(s)
Yujiro Toyoshima, Naoki Okada, Huihui Xiang, Satoshi Terada, Shuhei Kii, Yosuke Ohno, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Organizer
第45回 日本免疫学会学術集会
Place of Presentation
沖縄コンベンションセンター、ラグナガーデンホテル(沖縄県・宜野湾市)
Year and Date
2016-12-05
Related Report
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[Presentation] IL-6による免疫抑制メカニズムの解明と新規大腸がん肝転移治療への応用2016
Author(s)
豊島雄二郎, 北村秀光, 大野陽介, 寺田聖, 項慧慧, 市川伸樹, 吉田雅, 本間重紀, 川村秀樹, 高橋典彦, 武冨紹信
Organizer
第27回 日本消化器癌発生学会総会
Place of Presentation
城山観光ホテル(鹿児島県・鹿児島市)
Year and Date
2016-09-15
Related Report
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[Presentation] IL-6と関連したマイクロRNAの新規機能と担がん生体におけるバイオマーカーとしての有用性2016
Author(s)
豊島雄二郎, 大野陽介, 大竹淳矢, 寺田聖, 項慧慧, 岡田尚樹, 木井修平, 本間重紀, 川村秀樹, 高橋典彦, 武冨紹信, 北村秀光
Organizer
第8回 血液疾患免疫療法学会
Place of Presentation
北海道大学医学部学友会館「フラテ」(北海道・札幌市)
Year and Date
2016-09-03
Related Report
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