2006 Fiscal Year Final Research Report Summary
Regulation and Control of Immune Surveillance
| Project/Area Number |
15078204
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
MINATO Nagahiro Kyoto University, Graduate School of Biostuclies, Dept of Immunology and Cell Biology, Professor, 生命科学研究科, 教授 (40137716)
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| Co-Investigator(Kenkyū-buntansha) |
服部 雅一 京都大学, 生命科学研究科, 助教授 (40211479)
田中 義正 京都大学, 生命科学研究科, 助手 (90280700)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Immune surveillance / Tumor immunity / Leukemia / Immune suppression / SPA-1 / Tumor immunotherapy / T cell responsiveness / Memory T cells |
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| Research Abstract |
In this project, we aimed to study on the immunological surveillance mechanisms against tumor cells using naturally occurring tumor models in mice. The major achievements were as follows. (0 We found that SPA-1 KO mice naturally develop a spectrum of myeloproliferative disorders including chronic myeloid leukemia of long latency. The diseases highly resembled human myeloproliferative diseases, and SPA-1 KO mice were considered to provide an excellent model to study the roles of immune system during the naturally occurring malignancy (2) It was found that SPA-1 KO mice gradually developed CD4 T cell dysfunction preceding the leukemia development, and it was suggested that the T cell dysfunction during the preleukemic stage might contribute to the frank leukemia development (3) After overt development of systemic leukemia, the mice rapidly developed severe CD4 T cell unresponsiveness. This was ascribed to the progressive increase in PD-1+ CD4 T cells with memory phenotype, which were totally refractory to the TCR stimulation. Although exact mechanisms for the T cell unresponsiveness remained to be investigated, it was strongly suggested that marked increase in such a refractory T cell population contributed to the rapid progression of systemic leukemia leading to death. Future understanding of the mechanisms for leukemia cells to induce the T cell unresponsiveness and the development of the means to counteract the phenomenon should provide a hopeful approach to rescue the immune surveillance against tumor cells for controlling malignancy
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Research Products
(46 results)
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[Journal Article] Intestinal tumors inactivated in TGF-b signaling secrete CCL9 and recruit CCR1+ myeloid cells that help invasion.2007
Author(s)
Kitamura, T., Kometani, K., Hashiba, H., Matsunaga, A., Miyoshi.H., Hosogi, H., Aoki, M., Oshima, M., Hattori, M., Takabayashi, A., Minato, N., Taketo, M.
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Journal Title
Nature Gen. 39
Pages: 467-475
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PD-Ll and tumor-infiltrating CD8+ T lymphocytes are independent prognostic factors of human ovarian cancer.2007
Author(s)
Hamanishi J., Mandai, M., Iwasaki, M., Okazaki.T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K, Minato, N., Honjo, T., Fujii, S.
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Journal Title
Proc. Natl. Acad. Sci. USA. 104
Pages: 3360-3365
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from claudin-expressing cells.2007
Author(s)
Hamazaki, Y, Fujita, H, Kobayashi, T, Choi, Y, H. Scott, Matsumoto, M, Minato, N.
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Journal Title
Nature Immunol. 8
Pages: 304-311
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of SPA-1 in phenotypes of CML induced by BCR-ABL-expressing hematopoietic progenitors in mouse model.2006
Author(s)
Kometani, K., Kawamata, S., Shinozuka, Y., Era, T., Taniwaki, M., Hattori, M., Minato, N.
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Journal Title
Cancer Res. 66
Pages: 9967-9976
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of CD 166 in the activation of human ye, T cells by tumor cells sensitized with nonpeptide antigens.2006
Author(s)
Kato, Y., Tanaka, Y., Hayashi, M., Kita, S., Okawa, K., Minato, N.
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Journal Title
J.Immunol. 177
Pages: 877-884
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Rapl Signal Controls B Cell Receptor Repertoire and Generation of Self-reactive B1 Cells2006
Author(s)
Ishida, D., Su, L., Shinozuka, Y., Tamura, A., Katayama, Y., Kawai, Y., Wang, S-F, Taniwaki, M., Hamazaki, Y., Hattori, M., Minato, N.
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Journal Title
Immunity 24
Pages: 417-427
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] BCR/ABL and IL-3 activate Rap1 to stimulate B-Raf/MEK/Erk and Akt signaling pathways and to regulate proliferation, apoptosis, and adhesion.2006
Author(s)
Jin, A., Kurosu, T., Tsuji, K., Mizuchi, D., Arai, A., Fujita, H., Hattori, M., Minato, N., Miura, 0.
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Journal Title
Oncogene 20
Pages: 4332-4340
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prethymic stage of T cell development defined by the expression of paired immunoglobulin-like receptors.2005
Author(s)
Masuda, K., Kubagawa, H., Cooper, M.D., Kakugawa, K., Hattori, M., Kageyama, R., Minato, N., Katsura, Y., H.Kawamoto.
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Journal Title
EMBO J. 24
Pages: 4052-4060
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Minato-Hes-1 directly controls cell proliferation through the transcriptional repression of p27Kipl.2005
Author(s)
Murata, K, M.Hattori, N, Hirai, Y, Shinozuka, H, Hirata, R, Kageyama, T, Sakai, N
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Journal Title
Mol.Cell.Biol. 25
Pages: 4262-4271
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Thymic anlage is colonized by progenitors restricted to T, NK and dendritic cell lineages.2005
Author(s)
Masuda, K., Itoi, M., Amagai, T., Minato, N., Katsura, Y., Kawamoto, H.
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Journal Title
J.Immuno1. 174
Pages: 2525-2532
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 1 Bromodomain protein Brd4 binds to the GTPase activating SPA-1 modulating its activity and subcellular localization.2004
Author(s)
Farina, A., Hattori, M., Qin, J., Nakatani, Y., Minato, N., Ozato, K.
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Journal Title
Mol.Cell.Biol. 24
Pages: 9059-9069
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes.2004
Author(s)
Kawada, K., Sonoshita, M., Takabayashi, A., Yamaoka, Y., Inaba, K., Minato, N, Oshima, M., Taketo, M.
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Journal Title
Cancer Res. 64
Pages: 4010-4117
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of the earliest prethymic T cell progenitors in murine fetal blood.2004
Author(s)
Ikawa, T., Masuda, K., Lu, M., Minato, N., Katsura, Y., Kawamoto, H.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] T/NK bipotential progenitors in the thymus retain the potential to generate dendritic cells.2003
Author(s)
Shen, H-Q, Lu, M., Ikawa, T., Masuda, K., Ohmura, K., Minato, N., Katsura, Y., Kawamoto, H.
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Journal Title
J. Immunol. 171
Pages: 3401-3406
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathyin PD-1 deficient mice.2003
Author(s)
Okazaki, T., Tanaka, Y., Nishio, R., Mitsui, T., Mizoguchi, A., Jian, W., Ishida, M., Matsumori, A., Minato.N, Honjo, T.
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Journal Title
Nature Med. 9
Pages: 1477-1483
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Myeloproliferative stem cell disorders by deregulated Rapl activation in SPA-1-deficient mice.2003
Author(s)
Ishida D, Kometani, K., Yang, H, Kakugawa, K., Masuda, K, Iwai, K, Suzuki, M, Itohara, S, Nakahata, T, Hiai, H, Kawamoto, H., Hattori, M, Minato, N.
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Journal Title
Cancer Cell 4
Pages: 55-65
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of the ubiquitin-protein ligase that recognizes heme-oxidized IRP22003
Author(s)
Yamanaka, K., Ishikawa, H., Saitoh, K., Megumi, Y., Rouault, T., Morishima, I., Minato, N., Ishimori, K., Iwai, K.
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Journal Title
Nature Cell Bio1. 5
Pages: 336-340
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Antigen-driven T cell anergy and defective memory T cell response via deregulated Rapl activation in SPA-1-deficient mice.
Author(s)
Ishida, D., Yang, H., Masuda, K., Uesugi, K., Kawamoto, H., Hattori, M., Minato.N.
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Journal Title
Proc. Natl. Acad. Sci. USA 100
Pages: 10919-10924
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 2003.., and Minato, N. AF-6 negatively regulates integrin-mediated cell adhesion by binding both Rap1GTP and Rapl GTPase-activating proteins and enhancing Rapl inactivation.
Author(s)
Su, L., Hattori, M., Moriyama, M., Murata, N., Harazaki, M., Kaibuchi, K
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Journal Title
J. Biol. Chem. 278
Pages: 15232-15238
Description
「研究成果報告書概要(欧文)」より
