Reversion of exhausted T cells in tumor microenvironment
Project/Area Number |
26670237
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Immunology
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Research Institution | Okayama University |
Principal Investigator |
Udono Heiichiro 岡山大学, 医歯(薬)学総合研究科, 教授 (50260659)
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 免疫疲弊 / CD8T細胞 / 腫瘍微小環境 / メトホルミン / エフェクター・メモリー / AMPK / アポトーシス / サイトカイン |
Outline of Final Research Achievements |
Elevation of glycolysis in CD8 tumor infiltration lymphocyte (CD8TIL) was found by metformin (Met) administration. Also, mature CD8T cells differentiated from naive CD8T cells by in vitro TCR stimulation revealed enhanced glycolysis as well as oxidative phosphorylation by Met-treatment. Intestinal micro flora was not altered by Met. Significant reduction of Treg in tumors was also observed by Met. Inducible Treg (iTreg) differentiated from naive CD4T cells by TCR stimulation and TGFbeta was reduced in number and suppressive function by Met-treatment. Furthermore, reduction of MDSC in number, especially, G-MDSC rather than M-MDSC, was prominent in tumor tissue by Met. Also, increase of M1/M2 macrophage ration was observed by Met. It is clear that Met-administration dramatically changes tumor microenvironment towards favorable state for anti-tumor immunity.
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Report
(3 results)
Research Products
(27 results)
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[Journal Article] The induction of antigen-specific CTL by in situ Ad-REIC gene therapy.2016
Author(s)
Ariyoshi Y, Watanabe M, Eikawa S, Yamazaki C, Sadahira T, Hirata T, Araki M, Ebara S, Nasu Y, Udono H, Kumon H.
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Journal Title
Gene Ther.
Volume: gt.2016.7
Issue: 5
Pages: 408-414
DOI
Related Report
Peer Reviewed / Open Access
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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 and Tracking of NY-ESO-1-Specific CD8+ T Cells by High-Throughput T Cell Receptor β (TCRB) Gene Rearrangements Sequencing in a Peptide-Vaccinated Patient.2015
Author(s)
Miyai M, Eikawa S, Hosoi A, Iino T, Matsushita H, Isobe M, Uenaka A, Udono H, Nakajima J, Nakayama E, Kakimi K.
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Journal Title
PLoS One
Volume: 10(8)
Issue: 8
Pages: e0136086-e0136086
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse2014
Author(s)
Ichiyanagi, T., Ichiyanagi, K., Ogawa, A., Kuramochi-Miyagawa, S., Nakano, T., Chuma, S., Sasaki, H.
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Journal Title
Nucleic Acids Res
Volume: 42
Issue: 19
Pages: 11903-11
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 変貌するがん免疫治療2016
Author(s)
鵜殿平一郎
Organizer
熊本呼吸器フォーラム分科会
Place of Presentation
ホテルニューオータニ熊本(熊本)
Year and Date
2016-02-18
Related Report
Invited
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