Comprehensive study on IL-27, one of the IL-12 family cytokines, aiming at its clinical application for cancer immunotherapy
Project/Area Number |
18K07333
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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 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Tokyo Medical University |
Principal Investigator |
Xu Mingli 東京医科大学, 医学部, 客員講師 (80597964)
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Co-Investigator(Kenkyū-buntansha) |
善本 隆之 東京医科大学, 医学部, 教授 (80202406)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | IL-27 / がん治療 / 慢性骨髄性白血病 / BCR-ABL / 抗腫瘍作用 / CML / がん治療応用 / 骨髄由来免疫抑制細胞 |
Outline of Final Research Achievements |
A number of evidence reveled that IL-27 exerts antitumor effects through multiple mechanism, while it was also reported that IL-27 promotes proliferation of human leukemic cell lines. In addition, we previously demonstrated that IL-27 directly acts on hematopoietic stem cells (HSCs). Herein, we investigated the effects of exogenous IL-27 on the development of chronic myeloid leukemia (CML) using its mouse model, that is established by transferring causative gene BCR-ABL-transduced HSCs into irradiated mice. The results suggest that exogenous IL-27 activated CD8+ T cells and induced apoptosis of BCR-ABL+CML stem cells, which were shown using IL-27-transgenic mice. We also investigated the effects of endogenous IL-27 on the development of CM by transferring WSX-1-BCR-ABL+HSCs into wild-type mice. The results suggest that endogenous IL-27 directly acted on BCR-ABL+CML stem cells and inhibited their proliferation. These results may suggest its inhibitory effect on CML stem cells.
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Academic Significance and Societal Importance of the Research Achievements |
がんは、今や国民の半数が罹患し、死因の1/3を占める深刻な病気となっている。今日、免疫チェックポイント阻害薬やキメラ抗原受容体T細胞(CAR-T)療法などのがん免疫療法が注目されているが、治療効果に個人差があることや特定のがんにしか効かないなど、改善が迫られている。そこで、これらのがん免疫療法と、がんワクチン療法、サイトカイン療法などと併用し最善の治療方法を確立することが必要である。サイトカイン療法は、その副作用が大きいことが臨床応用への大きな妨げになっている。IL-12ファミリーサイトカインの1つIL-27は、比較的副作用が少なく強い抗腫瘍活性を示す報告が我々の報告を含め多数ある。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] EBV-induced gene 3 augments IL-23Rα protein expression through a chaperone calnexin.2020
Author(s)
Mizoguchi I, Ohashi M, Hasegawa H, Chiba Y, Orii N, Inoue S, Kawana C, Xu M, Sudo K, Fujita K, Kuroda M, Hashimoto S, Matsushima K, and Yoshimoto T.
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Journal Title
J Clin Invest.
Volume: 130(11)
Issue: 11
Pages: 6124-6140
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Necroptosis of intestinal epithelial cells induces type 3 innate lymphoid cell-dependent lethal ileitis.2019
Author(s)
Shindo R, Ohmuraya M, Komazawa-Sakon S, Miyake S, Deguchi Y, Yamazaki S, Nishina T, Yoshimoto T, Kakuta S, Koike M, Uchiyama Y, Konishi H, Kiyama H, Mikami T, Moriwaki K, Araki K, Nakano H.
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Journal Title
iScience
Volume: 15
Pages: 536-551
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Plasmacytoid dendritic cells protect against immune-mediated acute liver injury via IL-35.2019
Author(s)
Koda Y, Nakamoto N, Chu P, Ugamura A, Teratani T, Shiba S, Taniki N, Sujino T, Miyamoto K, Mikami Y, Suzuki T, Yamaguchi A, Morikawa R, Sato K, Yoshimoto T, Kanai K.
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Journal Title
J Clin Invest
Volume: 129(8)
Issue: 8
Pages: 3201-3213
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protective effects against tumors and infection by IL-27 through promotion of expansion and differentiation of hematopoietic stem cells into myeloid progenitors.2018
Author(s)
Orii N, Mizoguchi I, Chiba Y, Hasegawa H, Ohashi M, Xu M, Nagai T, Ochiai M, Mochizuki Y, Owaki T, Yoshimoto T.
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Journal Title
Oncoimmunology
Volume: -
Issue: 5
Pages: e1421892-e1421892
DOI
Related Report
Peer Reviewed
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[Journal Article] Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases.2018
Author(s)
Chiba Y, Mizoguchi I, Hasegawa H, Ohashi M, Orii N, Nagai T, Sugahara M, Miyamoto Y, Xu M, Owaki T, Yoshimoto T.
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Journal Title
Cell. Mol. Life Sci.
Volume: 75
Issue: 8
Pages: 1363-1376
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Protective role for IL-27 in the development of mouse chronic myeloid leukemia model.2018
Author(s)
Orii, N., Mizoguchi, I., Chiba, Y., Hasegawa, H., Xu, M., Ochiai, N., Mochizuki, Y., Owaki, T., and Yoshimoto, T.
Organizer
The 45th NATITO CONFERENCE ON Immunological and Molecular Bases for Cancer Immunotherapy
Related Report
Int'l Joint Research
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[Presentation] Antitumor effects of IL-27 against a mouse chronic myeloid leukemia (CML) model.2018
Author(s)
Orii, N., Hasegawa, H., Xu, M., Mizoguchi, I., Yoshida, H., and Yoshimoto, T.
Organizer
第182回東京医科大学医学会総会
Related Report
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[Presentation] Antitumor effects of IL-27 against a mouse chronic myeloid leukemia model.2018
Author(s)
Orii, N., Hasegawa, H., Xu, M., Mizoguchi, I., Yoshida, H., and Yoshimoto, T.
Organizer
第47回日本免疫学会総会・学術集会
Related Report