Development of novel classification of colorectal cancer for immunotherapy
| Project/Area Number |
26670581
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | National Cancer Center Japan (2015)
Osaka University (2014) |
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Principal Investigator |
Nishikawa Hiroyoshi 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (10444431)
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| Co-Investigator(Renkei-kenkyūsha) |
DOKI Yuichiro 大阪大学, 大学院医学研究科, 教授 (20291445)
HONDA Kenya 理化学研究所, 統合生命医科学研究センター, チームリーダー (60334231)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 免疫学 / 制御性T細胞 / 大腸癌 / エフェクターT細胞 |
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| Outline of Final Research Achievements |
Human FOXP3+CD4+ T cells were composed of three distinct subpopulations: CD45RA+FOXP3lo+ naive Tregs, CD45RA-FOXP3hi+ effector Tregs, and CD45RA-FOXP3lo+ non-Tregs. While FOXP3+ T cell infiltration is a poor prognosis marker in many cancers, the significance of FOXP3 T cells in colorectal cancers(CRC) has been controversial. While CRC were commonly infiltrated by suppression-competent FOXP3hi Treg cells,they were divided into two groups by the degree of additional infiltration of FOXP3lo non-suppressive T cells. Such cells were induced by IL-12 and TGF-B and were correlated with tumor invasion of intestinal bacteria. Functionally distinct subpopulations of tumor-infiltrating FOXP3+ T cells oppositely contribute to determining CRC prognosis. Depletion of FOXP3hi Treg cells from tumor tissues to augment anti-tumor immunity can be an effective treatment of CRC and other cancers, while strategies to locally increase FOXP3lo non-Treg cells could be tumor-suppressive and -preventive.
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Report
(3 results)
Research Products
(59 results)
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[Journal Article] Hypomethylation of the Treg-specific demethylated region in FOXP3 is a hallmark of the regulatory T-cell subtype in adult T-cell leukemia2016
Author(s)
Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A
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Journal Title
Cancer Immunol Res
Volume: 4
Issue: 2
Pages: 136-145
DOI
Related Report
Peer Reviewed
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[Journal Article] Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients.2015
Author(s)
2.Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, Doi T, Suzuki S, Isobe M, Funakoshi T, Kakimi K, Nishikawa H, Udono H, Oka M, Ueda R, Nakayama E.
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Journal Title
Clin Cancer Res.
Volume: 21
Issue: 19
Pages: 4327-36
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals.2014
Author(s)
Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S.
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Journal Title
Science
Volume: 346
Issue: 6216
Pages: 1536-40
DOI
Related Report
Peer Reviewed
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[Journal Article] Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation.2014
Author(s)
Mastumoto, M., Baba, A., Yokota, T., Nishikawa, H., Ohkawa, Y., Kayama, H., Kallies, A., Nut, S. L., Sakaguchi, S., Takeda, K., Kurosaki, T., and Baba, Y.
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Journal Title
Immunity
Volume: 41
Issue: 6
Pages: 1040-1051
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease.2014
Author(s)
Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali D, Kappler J, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S.
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Journal Title
Science
Volume: 346
Issue: 6207
Pages: 363-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Vaccination With NY-ESO-1 Overlapping Peptides Mixed With Picibanil OK-432 and Montanide ISA-51 in Patients With Cancers Expressing the NY-ESO-1 Antigen2014
Author(s)
Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.
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Journal Title
J Immunother
Volume: 37(2)
Issue: 2
Pages: 84-92
DOI
Related Report
Peer Reviewed
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