Analysis of activation pathways and functional heterogeneity of macrophages - beyond M1/M2 paradigm
Project/Area Number |
25293089
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Human pathology
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Research Institution | Kumamoto University |
Principal Investigator |
TAKEYA MOTOHIRO 熊本大学, 大学院生命科学研究部, 教授 (90155052)
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Co-Investigator(Kenkyū-buntansha) |
KOMOHARA YOSHIHIRO 熊本大学, 大学院生命科学研究部, 准教授 (40449921)
OHNISHI KOJI 熊本大学, 大学院生命科学研究部, 助教 (40613378)
FUJIWARA YUKIO 熊本大学, 大学院生命科学研究部, 講師 (70452886)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
|
Keywords | M1/M2マクロファージ / 腫瘍随伴マクロファージ / ヒト悪性腫瘍 / がん幹細胞 / CD163 / CD204 / Stat3 / corosolic acid / M2マクロファージ / 患者予後 / 腫瘍増殖 / CD169 / 天然化合物 / onionin A / マクロファージ / オルタナティブ活性化 |
Outline of Final Research Achievements |
Tumor-associated macrophages of M2-type (M2-TAM) were considered to play an important role in the maintenance of stemness in a human clear cell renal cell carcinoma. In adult T cell leukemia/lymphoma, density of CD163-positive M2-TAM was associated with poor prognosis of patients, whereas CD204-positive M2-TAM was not, indicating the functional difference of CD163-positive TAMs and CD204-positive TAMs. Increased number of CD169-positive sinus macrophages in the regional lymph nodes of colon cancer and malignant melanoma was associated with favorable prognosis of the patients. Since it is positively correlated with the number of CD8-positive T cells in tumor tissues, CD169-positive sinus macrophages were considered to be involved in the establishment of anti-tumor immunity. It was found that corosolic acid, a natural compound that suppresses M2-macrophage differentiation, inhibits tumor cell growth via suppressing the Stat3 activation of both tumor cells and macrophages.
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Report
(4 results)
Research Products
(135 results)
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[Journal Article] Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma.2016
Author(s)
Ma C, Komohara Y, Ohnishi K, Shimoji T, Kuwahara N, Sakumura Y, Matsuishi K, Fujiwara Y, Motoshima T, Takahashi W, Yamada S, Kitada S, Fujimoto N, Nakayama T, Eto M, Takeya M.
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Journal Title
Cancer Sci.
Volume: Epub
Issue: 5
Pages: 700-707
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA-DR lower fraction of monocytes in patients with renal cell carcinoma.2016
Author(s)
Motoshima T, Komohara Y, Horlad H, Tsukamoto H, Fujita M, Saito Y, Tanoue K, Kasejima Y, Sugiyama Y, Kawano Y, Nishimura Y, Takeya M, Eto M.
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Journal Title
Oncol Lett
Volume: 11
Pages: 1911-1916
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma.2015
Author(s)
Saito Y, Ohnishi K, Miyashita A, Nakahara S, Fujiwara Y, Horlad H, Motoshima T, Fukushima S, Jinnin M, Ihn H, Takeya M, Komohara Y.
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Journal Title
Cancer Immunol Res.
Volume: 3
Issue: 12
Pages: 1356-1363
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cyclic Sulfoxides-Garlicnins K<sub>1</sub>, K<sub>2</sub>, and H<sub>1</sub>-Extracted from <i>Allium sativum</i>2015
Author(s)
Nohara T, Fujiwara Y, Komota Y, Kondo Y, Saku T, Yamaguchi K, Komohara Y, Takeya M
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Journal Title
Chemical and Pharmaceutical Bulletin
Volume: 63
Issue: 2
Pages: 117-121
DOI
NAID
ISSN
0009-2363, 1347-5223
Related Report
Peer Reviewed / Open Access
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[Journal Article] The coordinated actions of TIM-3 on cancer and myeloid cells in the regulation of tumorigenicity and clinical prognosis in clear cell renal cell carcinomas.2015
Author(s)
Komohara Y, Morita T, Annan DA, Horlad H, Ohnishi K, Yamada S, Nakayama T, Kitada S, Suzu S, Kinoshita I, Dosaka-Akita H, Akashi K, Takeya M, Jinushi M
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Journal Title
Cancer Immunol Res
Volume: -
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation2014
Author(s)
Ishimoto T, Sugihara H, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, Okabe H, Hidaka K, Yokoyama N, Miyake K, Yoshikawa M, Nagano O, Komohara Y, Takeya M, Saya H, Baba H.
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Journal Title
Carcinogenesis
Volume: 35(5)
Issue: 5
Pages: 1003-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.2014
Author(s)
Khan S, Rahman H N A, Okamoto T, Matsunaga T, Fujiwara Y, Sawa T, Yoshitake J, Ono K, Ahmed K A, Rahaman M d M, Oyama K, Takeya M, Ida T, Kitamura Y, Fujii S, Akaike T.
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Journal Title
Sci. Rep.
Volume: (印刷中)
Issue: 1
Pages: 4680-4680
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Acyclic Sulfides, Garlicnins L-1-L-4, E, and F, from Allium sativum.2014
Author(s)
Nohara T, Fujiwara Y, Ikeda T, Yamaguchi K, Manabe H, Murakami K, Ono M, Nakano D, Kinjo J
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Journal Title
Chem Pharm Bull (Tokyo)
Volume: 62
Pages: 477-482
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Acantholactam and pre-neo-kauluamine, manzamine-related alkaloids, from the Indonesian marine sponges, Acanthostrongylophora ingens.2014
Author(s)
A. H. El-Desoky, H. Kato, K. Eguchi, T. Kawabata, Y. Fujiwara, F. Losung, R. E. P. Mangindaan, N. J. de Voogd, M. Takeya, H. Yokosawa, S. Tsukamoto
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Journal Title
J. Nat. Prod.
Volume: 77
Issue: 6
Pages: 1536-1540
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Isolation and Characterization of New Onionins A2 and A3 from Allium cepa, and of Onionins A1, A2, and A3 from Allium fistulosum.2014
Author(s)
Nohara T, Fujiwara Y, Kudo R, Yamaguchi K, Ikeda T, Murakami K, Ono M, Kajimoto T, Takeya M
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Journal Title
Chem Pharm Bull (Tokyo)
Volume: 62
Pages: 1141-1145
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overexpression of CD163, CD204 and CD206 on alveolar macrophages in the lungs of patients with severe chronic obstructive pulmonary disease.2014
Author(s)
Kaku Y, Imaoka H, Morimatsu Y, Komohara Y, Ohnishi K, Oda H, Takenaka S, Matsuoka M, Kawayama T, Takeya M, Hoshino T
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Journal Title
PLoS One
Volume: 30
Issue: 1
Pages: e87400-e87400
DOI
Related Report
Peer Reviewed
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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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[Presentation] Clinical significance of CD169-positive lymph node macrophages in human malignant tumors.2014
Author(s)
Koji Ohnishi, Yoichi Saito, Yoshihiro Komohara, Yuji Miyamoto, Satoshi Fukushima, Munekage Yamaguchi, Hideo Baba, Hironobu Ihn, Hidetaka Katabuchi, Motohiro Takeya
Organizer
2014 ASCO Annual Meeting
Place of Presentation
McCormick Place Chicago, Illinois, USA
Year and Date
2014-05-30 – 2014-06-03
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