Reverse Translational Research for Understanding immune response in the Tumor and Identification of Biomarkers
Project/Area Number |
24501329
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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 |
Tumor immunology
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Research Institution | The University of Tokyo |
Principal Investigator |
KAKIMI KAZUHIRO 東京大学, 医学部附属病院, 特任教授 (80273358)
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Co-Investigator(Kenkyū-buntansha) |
UEHA Satoshi 東京大学, 医学(系)研究科, 講師 (00447385)
MATSUSHITA Hirokazu 東京大学, 医学部附属病院, 特任講師 (80597782)
阿部 淳 東京大学, 医学(系)研究科(研究院), 助教 (50581831)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | CTL / 免疫抑制 / PD-1 / γδ T細胞 / 抗腫瘍免疫応答 / がん免疫 / 樹状細胞 / γδT細胞 / MDSC / スニチニブ / IFN-γ / 細胞周期 / 胃がん / 癌性腹膜炎 / 細胞傷害性T細胞 / 骨髄性抑制細胞 / DC / 免疫治療 |
Outline of Final Research Achievements |
To develop novel effective cancer immunotherapy, we performed‘Reverse TR’ study using clinical samples and information from patients who received cancer immunotherapy at the University of Tokyo Hospital. To identify the biomarkers that can help us select patients who are expected to have benefit from immunotherapy, we integrate clinical study and basic immunological study. Many clinical samples were collected by NY-ESO-1 peptide or dendritic cell vaccines and γδ T cell transfer therapy. While some good clinical responses were obtained in certain patients, others did not show such clinical responses despite the induction of anti-tumor immune response. In murine model, we demonstrated that CTLs produce IFN-γ and mediate anti-tumor activity, but they simultaneously induce counter-regulatory immunosuppressive mechanisms in the tumor. These results suggest that strategies to regulate CTL-induced immunosuppressive microenvironment would improve the efficacy of cancer immunotherapy.
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1immune checkpoint antibody treatment in mice.2015
Author(s)
Ueha S, Yokochi S, Ishiwata Y, Ogiwara H, Chand K, Nakajima T, Hachiga K,Shichino S, Terashima Y, Toda E, Shand FH, Kakimi K, Ito S, Matshushima K.
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Journal Title
Cancer Immunol Res.
Volume: Epub ahead of print
Issue: 6
Pages: 631-640
DOI
Related Report
Peer Reviewed
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[Journal Article] Granulocyte macrophage colony-stimulating factor as a predictor of the response of metastatic renal cell carcinoma to tyrosine kinase inhibitor therapy.2014
Author(s)
Yamada D, Matsushita H, Azuma T, Nakagawa T, Nagata M, Yamada Y, Suzuki M, Fujimura T, Fukuhara H, Kume H, Homma Y, Kakimi K.
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Journal Title
Mol Clin Oncol
Volume: 2
Issue: 6
Pages: 1023-27
DOI
Related Report
Peer Reviewed / Open Access
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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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[Journal Article] Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells.2013
Author(s)
Shimizu K, Mizuno T, Shinga J, Asakura M, Kakimi K, Ishii Y, Masuda K, Maeda T, Sugahara H, Sato Y, Matsushita H, Nishida K, Hanada K, Dorrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R, Fujii S.
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Journal Title
Cancer Res.
Volume: 73(1)
Issue: 1
Pages: 62-73
DOI
Related Report
Peer Reviewed
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[Journal Article] Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.2013
Author(s)
Eikawa, S., Kakimi, K., Idobe, M., Kuzushima, K., Luescher, I., Ohue, Y., Ikeuchi, K., Uenaka, A., Nishikawa, H., Udono, H., Oka, M., and Nakayama, E.
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Journal Title
Int. J. Cancer
Volume: 132(2)
Issue: 2
Pages: 345-54
DOI
Related Report
Peer Reviewed
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[Presentation] High expression of Heat Shock Protein 105 Predicts Favorable Prognosis in Bladder Cancer Patients Treated by a Radical Cystectomy2012
Author(s)
Yutaka Enomoto, Haruki Kume, Hiroshi Fukuhara, Tetsuya Fujimura, Motofumi Suzuki, Hiroaki Nishimatsu, Akira Ishikawa, Hirokazu Matsushita, Kazuhiro Kakimi, Yukio Homma.
Organizer
11th Asian Congress of Urology
Place of Presentation
Pattaya, Thailand
Related Report
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[Presentation] Dendritic Cell-based Immunotherapy Combined with Sunitinib for Metastatic Renal Cell Carcinoma2012
Author(s)
Yutaka Enomoto, Haruki Kume, Hiroshi Fukuhara, Tetsuya Fujimura, Motofumi Suzuki, Hiroaki Nishimatsu, Akira Ishikawa, Hirokazu Matsushita, Kazuhiro Kakimi, Yukio Homma.
Organizer
The 32nd Congress of the Societe Internationale d’Urokigue,
Place of Presentation
Fukuoka,Japan
Related Report
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