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2006 Fiscal Year Final Research Report Summary

Immune Surveillance, Its cellular and molecular basis, regulation and maintenance

Research Project

Project/Area Number 15078101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRIKEN (2004-2006)
Kyushu University (2003)

Principal Investigator

WATANABE Takeshi  RIKEN, Immune Surveillance Research Unit, Unit Leader -> 独立行政法人理化学研究所, 免疫監視機構研究ユニット, ユニットリーダー (40028684)

Co-Investigator(Kenkyū-buntansha) MINATO Naeahiro  Kyoto University, Graduate School of Biostudies, Professor, 大学院生命科学研究科, 教授 (40137716)
MATSUSHIMA Koji  University of Tokyo, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (50222427)
SAITO Takashi  Laboratory for Cell Signaling, Group Leader, 免疫シグナル研究グループ, グループディレクター (50205655)
KOYASU Shigeo  Keio University, School of Medicine, Professor, 医学部, 教授 (90153684)
YAMAMOTO Kazuhiko  University of Tokyo, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (80191394)
Project Period (FY) 2003 – 2006
Keywordsimmune surveillance / spatio-temporal regulation / thymus, bone marrow, lymph nodes / recognition and diversity / memory / signal transduction / autoimmune diseases / regeneration,
Research Abstract

The concept of "Immune Surveillance" was first proposed almost 50 years ago as a mechanism for elimination of nascent cancer cells before they develop into clinically evident tumors. However, the fundamental nature of this concept has not yet been fully clarified at either the cellular or molecular level, even though remarkable progress has been made in tumor immunology. Not only in the control of cancer, Immune Surveillance system plays a crucial role in the prevention of severe infection as well as the regulation of autoreactive immune responses. The objective of this special project is to broadly develop the basic research concerning the structural basis of the immune surveillance system in mice and humans, the regulation and maintenance of the surveillance network, and its clinical significance.
Year 2006 was the last year of this 4-years-term project on the Immune Surveillance Mechanism. As one of the activities of the "Summation Group (Sokatsu-han)", we especially promoted the interaction between researchers in order to facilitate their research activities on the clarification of the cellular and molecular basis of immune surveillance mechanism as well as invention to repair and reinforcement of the surveillance in our body. During 2006, over 200 papers were published. Among them, 30 papers were published in Journals of IF : over 20, and 60 papers in Journals of IF :10-20. We held the Second International Symposium on the Immune Surveillance at Tokyo on February 14, 15, 2007. We invited 11 foreign speakers from US and Europe who have been extensively developing their research on immune surveillance. It was very successful. During 4 years, 600 papers were published. Among them, 205 papers were reported in the Journals of IF : over 10. Over 50 patents were applied. We held 3 major symposia including 2 international symposia.

Research Products

(59 results)

All 2007 2006 2005

All Journal Article Patent(Industrial Property Rights)

  • [Journal Article] Intestinal tumors inactivated in TGF-b signaling secrete CCL9 and recruit CCR1+ myeloid cells that help invasion.2007

    • Author(s)
      Kitamura, T.(他11名)
    • Journal Title

      Nature Genetics 39

      Pages: 467-475

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PD-1 and tumor-infiltrating CD8+ T lymphocytes are independent prognostic factors of human ovarian cancer2007

    • Author(s)
      Hamanisi, Y(他10名)
    • Journal Title

      Proc. Natl. Acad. Sci. USA 104

      Pages: 3360-3365

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from claudin-expressing cells2007

    • Author(s)
      Hamazaki, Y(他6名)
    • Journal Title

      Nature Immunology 8

      Pages: 304-311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of immune responses and hematopoiesis by the Rapl signal.2007

    • Author(s)
      Minato, N.(他2名)
    • Journal Title

      Adv. Immunol. 93

      Pages: 229-264

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.2007

    • Author(s)
      Ueha S, Matsushima, K et al.
    • Journal Title

      J Leukoc Biol. 81

      Pages: 176-185

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] SARA-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus.2007

    • Author(s)
      Kitabatake M, Matsushima, K et al.
    • Journal Title

      Vaccine 25

      Pages: 630-637

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Conbined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma : clinical safety.2007

    • Author(s)
      Nakamoto Y, Matsushima, K et al.
    • Journal Title

      Clin Exp Immunol. 147

      Pages: 296-305

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation.2007

    • Author(s)
      Suzuki, J-I.
    • Journal Title

      Blood. 109

      Pages: 168-175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular basis for pre-TCR-mediated autonomous signaling2007

    • Author(s)
      Yamasaki, S.
    • Journal Title

      Trends. Immunol. 28

      Pages: 39-43

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Artificial LNs induce potent secondary immune responses in naive and immunodeficient mice2007

    • Author(s)
      Okamoto N, Watanabe T他3名
    • Journal Title

      Journal of Clinical Investigation 117

      Pages: 997-1007

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of SPA-1 in phenotypes of CML induced by BCR-ABL-expressing hematopoietic progenitors in mouse model2007

    • Author(s)
      Kometani, K(他6名)
    • Journal Title

      Cancer Res. 66

      Pages: 9967-9976

    • Description
      「研究成果報告書概要(和文)」より
  • [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.Hosogi, H., Aoki, M., Oshima, M., Hattori, M., Takabayashi, A., Minato, N, Taketo, M.
    • Journal Title

      Nature Gen. 39

      Pages: 467-475

    • Description
      「研究成果報告書概要(欧文)」より
  • [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, 1, Fujii, S.
    • 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
  • [Journal Article] Medullary thymic epithelial cells expressing Aire represent ; unique lineage derived from claudin-expressing cells.2007

    • Author(s)
      Hamazaki, Y, Fujita, H, Kobayashi, T, Choi, Y, H. Scott, Matsumoto, M, Minato, N.
    • Journal Title

      INature Immunol. 8

      Pages: 304-311

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviate; graft-versus-host reaction associated inte and hematopoiesis by the Rap] signal. (Review)2007

    • Author(s)
      Minato, N, K.Kometani, M.Hattori.Regulation of immune responses Ueha S, et al.
    • Journal Title

      Adv. Immunol. 93

      Pages: 229-264

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intervention of MAdCAM-1 or Fractalkine alleviate; graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects.2007

    • Author(s)
      Ueha S, et al.
    • Journal Title

      J Leukoc Biol 81(1)

      Pages: 176-85

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] SARS-CoV spike protein-expressing recombinan vaccinia virus efficiently induces neutralizing antibodies in rabbit; pre-immunized with vaccinia virus.2007

    • Author(s)
      Kitabatake M, et al.
    • Journal Title

      Vaccine 25(4)

      Pages: 630-7

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Combined therapy of transcatheter hepatic arteria embolization with intratumoral dendritic cell infusion for hepatocellula] carcinoma : clinical safety..2007

    • Author(s)
      Nakamoto Y, et al.
    • Journal Title

      Clin Exp Immunol 147(2)

      Pages: 296-305

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The actir cloud induced by LFA-1-mediated outside-in signals lowers the thresholc for T-cell activation.2007

    • Author(s)
      Suzuki, J-I, Yamasaki, S., Wu, J., Koretzky, GA., Saito, T.
    • Journal Title

      LBlood. 109(1)

      Pages: 168-175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular basis for pre-TCR-mediatec autonomous signaling2007

    • Author(s)
      Yamasaki, S., Saito, T.
    • Journal Title

      Trends. Immunol. 28(1)

      Pages: 39-43

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Artificial lymph nodes induce potent secondary immune responses in na・e and immunodeficient mice2007

    • Author(s)
      Okamoto N., Watanabe T.(3 others)
    • Journal Title

      J. Clinical Invest. 117

      Pages: 997-1007

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Essentioal roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo.2006

    • Author(s)
      Ohteki T, Koyasu S他6名
    • Journal Title

      Journal of Experimental Medicine 203

      Pages: 2329-2338

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development.2006

    • Author(s)
      Yamasaki, S.
    • Journal Title

      Nat Immunol. 7

      Pages: 67-75

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Compartmentalization of signaling and degradation in the immunological synapse.2006

    • Author(s)
      Varma R, Saito T.他3名
    • Journal Title

      Immunity 25

      Pages: 117-127

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Critical role of MLL for the maintenance of memory T helper type 2 cell responses.2006

    • Author(s)
      Yamashita M, Nakayama T他6名
    • Journal Title

      Immunity 24

      Pages: 611-622

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunological synapse and microclusters; the site for recognition and activation of T cells2006

    • Author(s)
      Saito, T.
    • Journal Title

      Curr. Opin. Immunol. 18

      Pages: 305-313

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IRAK-4-a shared NK-kB activator in innate and acquired immunity.2006

    • Author(s)
      Suzuki, N.
    • Journal Title

      Trends. Immunol. 27

      Pages: 566-572

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The H1 histamine receptor regulates allergic lung response2006

    • Author(s)
      Bryce PJ, Watanabe T.他4名
    • Journal Title

      Journal of Clinical Investigation 116

      Pages: 1624-1632

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Alterations of sleep-wake behavioral characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice.2006

    • Author(s)
      Zhi-Li Huang, Watanabe T.他6名
    • Journal Title

      Proc. Natl. Acad. Sci. USA 103

      Pages: 4687-4692

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] BCR/ABL and IL-3 activate Rap1 to stimulate B-Raf/MEK/Erk and Akt signaling pathways and to regulate proliferation, apotosis and adhesion.2006

    • Author(s)
      Jin, A(他8名)
    • Journal Title

      Oncogene 20

      Pages: 4332-4340

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvament of CD166 in the activation of human gd T cells by tumor cells sensitized with nonpeptide antigens2006

    • Author(s)
      Kato, Y., (他5名)
    • Journal Title

      J. Immunol 177

      Pages: 877-884

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A critical role for the innate immune signaling molecule IRAK-4 in T cell acivation2006

    • Author(s)
      Suzuki N, Saito T他14名
    • Journal Title

      Science 311

      Pages: 1927-1932

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Rapl signal control B cell receptor repertoire and generation of self-reactive B1 cells.2006

    • Author(s)
      Ishida D, Minato N他9名
    • Journal Title

      Immunity 24

      Pages: 417-427

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clicical significance of RCAS1 as a biomarker of uterine cancer.2006

    • Author(s)
      Sonoda K., Watanabe T他6名
    • Journal Title

      Gynecologic Oncology 103

      Pages: 924-931

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cimetidine induces IL-18 production through H2-agonist acivity in monocytes.2006

    • Author(s)
      Takahashi, HK, Watanabe T他5名
    • Journal Title

      J. Pharmacological Science 70

      Pages: 450-453

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.2006

    • Author(s)
      Sakai N, Matsushima K et al.
    • Journal Title

      Proc Natl Acad Sci U S A. 103

      Pages: 14098-103

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein kinase.2006

    • Author(s)
      Wada T, Matsushima K et al.
    • Journal Title

      Am J Nephrol. 26

      Pages: 319-325

    • Description
      「研究成果報告書概要(和文)」より
  • [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.
    • Journal Title

      Cancer Res. 66

      Pages: 9967-9976

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] BCR/ABL and IL-3 activate Rap1 to stimulateB-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.
    • Journal Title

      Oncogene 20

      Pages: 4332-4340

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of CD166 in the activation of human yS T cells by tumor cells sensitized with nonpeptide antigens.2006

    • Author(s)
      Kato, Y., Tanaka, Y., Hayashi, M., Kita, S., Okawa, K., Minato, N.
    • Journal Title

      Mmmunol. 177

      Pages: 877-884

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A critical role of the innate immune signaling molecule 1RAK-4 in T cell activation.2006

    • Author(s)
      Suzuki N, Saito T. (14 others)
    • Journal Title

      Science 311

      Pages: 1927-1932

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rapi signal control B cell receptor repertoire and generation of self-reactive B1 cells.2006

    • Author(s)
      Ishida D., Minato N.(9 others)
    • Journal Title

      mmunity 24

      Pages: 417-427

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Essential roles of DC- derived IL-15 as a mediator of inflammatory responses in vivo2006

    • Author(s)
      Oteki T., Koyasu S.(6 others)
    • Journal Title

      J. of Exp. Medicine 203

      Pages: 2329-2339

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development.2006

    • Author(s)
      Yamasaki, S.Ishikawa, E., Sakuma, M., Ogata, K., Sakata-Sogawa, K., Hiroshima, M., Wiest, D.L., Tokunaga, M., Saito, T.
    • Journal Title

      Nat Immunol. 7(1)

      Pages: 67-75

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Compartmentalization of signaling and degradation in the immunological synapse2006

    • Author(s)
      Varma R., Saito T.(3 others)
    • Journal Title

      Immunity 25

      Pages: 117-127

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Critical role of MLL for the maintenance of memory T helper type 2 cell responses.2006

    • Author(s)
      Yamashita M., Nakayama T.(6 others)
    • Journal Title

      Immunity 24

      Pages: 611-622

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunological synapse and microclusters : the site for recognition and activation of T cells.2006

    • Author(s)
      Saito, T., Yokosuka, T.
    • Journal Title

      Cum Opin. Immunol 18(3)

      Pages: 305-313

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IRAK-4-a shared NK-KB activator in innate and acquired immunity.2006

    • Author(s)
      Suzuki, N., Saito, T.
    • Journal Title

      Trends. Immunol. 27(12)

      Pages: 566-572

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The H1 histamine receptor regulates allergic lung responses.2006

    • Author(s)
      Bryce PJ., Watanabe T.(4 others)
    • Journal Title

      J. Clinical Invest. 116

      Pages: 1624-1632

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Alteration of sleep-wake behavioral characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout.2006

    • Author(s)
      Huang Zhi-Li, Watanabe T. (6 others)
    • Journal Title

      Proc. Natl. Acad. Sci. USA 103

      Pages: 4687-4692

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical significance of RCAS1 as a biomarker of uterine cancer.2006

    • Author(s)
      Sonoda K., Watanabe T.(6 others)
    • Journal Title

      Gynecologic Oncology 103

      Pages: 924-931

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cimetidine induces IL-18 production through H2-agonist activity in Monocytes2006

    • Author(s)
      Takahashi HK, Watanabe T.(5 others)
    • Journal Title

      J. Pharmacological Science 70

      Pages: 450-453

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis.2006

    • Author(s)
      Sakai N, et al.
    • Journal Title

      1Proc Natl Acad Sci USA. 103(38)

      Pages: 14098-103

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reduction in Chronic Allograft Nephropathy by Inhibition of p38 Mitogen-Activated Protein Kinase.2006

    • Author(s)
      Wada T, et al.
    • Journal Title

      Am J Nephrol. 26(4)

      Pages: 319-25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 2型ヒスタミン受容体タンパクに結合し, かつ2型ヒスタミン受容体とヒスタミンの結合を阻止しうるモノクローナル抗体2007

    • Inventor(s)
      渡邊 武
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2007-054674
    • Filing Date
      2007-03-05
    • Application Year
      2007
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] NK細胞の機能調節剤およびそのスクリーニング法2006

    • Inventor(s)
      斉藤隆, 原博満
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2006-303073
    • Filing Date
      2006-11-08
    • Application Year
      2006
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 癌治療用人工リンパ節2006

    • Inventor(s)
      渡邊 武
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2006-331114
    • Filing Date
      2006-12-07
    • Application Year
      2006
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] クラスターを形成し得る細胞表面レセプターを有する細胞の活性化制御剤およびそのスクリーニング方法2005

    • Inventor(s)
      斉藤隆, 横須賀忠
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2005-298279
    • Filing Date
      2005-10-13
    • Application Year
      2005
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 人工リンパ節を用いた効率的な抗原特異的ハイブリドーマの作成法2005

    • Inventor(s)
      渡邊 武
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2005-357949
    • Filing Date
      2005-12-12
    • Application Year
      2005
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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