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Immune response and escape in human cancers

Research Project

Project/Area Number 16209013
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

SATO Noriyuki  Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (50158937)

Co-Investigator(Kenkyū-buntansha) TORIGOE Toshihiko  Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20301400)
ICHIMIYA Shingo  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (30305221)
SAHARA Hiroeki  Sapporo Medical University, School of Medicine, Assistant Professor, 臨海医学研究所, 講師 (10260762)
TAMURA Yasuaki  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (80322329)
KAMIGUCHI Kenjiro  Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (70363695)
池田 英之  札幌医科大学, 医学部, 講師 (40301494)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000)
Fiscal Year 2006: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2005: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2004: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Keywordscancer vaccine / survivin / SYT-SSX / HLA class I down regulation / immune escape / epigenetics / HAD inhibitor / HSP90 / エスケープ / ヒト癌免疫治療 / HLAクラス1 / HDAC / 抗原ペプチド / 腫瘍抗原 / β2ミクログロブリン / 免疫治療 / mAb / 癌抗原ペプチドワクチン / MHC I / II / CIITA / 病理標本
Research Abstract

The investigation of human tumor immunotherapy has remarkably advanced in the past decade. In our laboratory, human tumor antigens and their HLA-A24-restricted immunogenic peptide epitopes were determined to develop therapeutic and prophylactic human cancer vaccines. Among these peptides, survivin 2B peptide derived from survivin, an inhibitor of apoptosis protein (IAP), is immunogenic in more than 50 % of cancer patients with a wide variety of tumors, including colon, pancreas, lung, breast, urinary bladder and oral cancers. It is now under clinical and with careful immunological monitoring we will finally be able to know if these vaccines can work clinically.
To develop a potent clinical therapeutic protocol, the immunological tumor escape mechanism should be more thoroughly examined in human tumor materials. To this end, anti-HLA-A, B, and C allele-specific monoclonal antibody EMR8-5, which can be used in routine paraffin-embedded sections, was successfully established. Unexpectedly, our data indicated that a high percentage of human cancers, particularly breast and prostate cancers, lost HLA-class I molecules in their primary cancer tissues. We will discuss possibilities for resolution of this important old but yet new problem.
Although recent evidence has been accumulating for an important role of the heat shock proteins (HSPs) as so-called danger signals in initiating innate immunity and consequently activating acquired immunity, the precise immunological basis for this phenomenon remains to be elucidated. Our study indicated that certain HSP-chaperoned immunogenic peptides, particularly HSP90, could efficiently enter the cross-priming pathway in dendritic cells. Interestingly, this cross-priming was TAP-independent and followed endocytic pathways. We also showed that HSP90-chaperoned peptide complexes could work as a potential tumor therapeutic vaccine in the HLA-A24 transgenic mouse model.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005 2004 Other

All Journal Article (26 results) Book (4 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma.2007

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      J. Urol. 177

      Pages: 1269-1272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Mapping of susceptibility and protective loci tor acute GVHD in unrelated HLA-matcned bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22.2007

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

      Immunogenetics 59

      Pages: 99-108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an enaosomal pathway.2007

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

      J. Immunol. (in press )

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of endogenous MHC class II-restricted antigen presentation by tacrohmus (FK506) via FKBP51.2007

    • Author(s)
      Imai, A. et al.
    • Journal Title

      Eur. J. Immunol. 37(in press )

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Down-regulation of HLA class I antigen is an independent prognostic factor for clear cell renal cell carcinoma.2007

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      J.Urol. 177

      Pages: 1269-1272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22.2007

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

      Immunogenetics 59

      Pages: 99-108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an endosomal pathway2007

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

      J.Immunol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP512007

    • Author(s)
      Imai, A. et al.
    • Journal Title

      Eur.J.Immunol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5.2006

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

      Cancer Science 97

      Pages: 1374-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Effect of human leukocyte antigen class I expression of tumor cells on outcome of mtravesical instillation of bacillus Calmette-Guerm immunotherapy for bladder cancer.2006

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      Clin. Cancer Res. 12

      Pages: 4641-4644

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of human leukocyte antigen class 1 expression of tumor cells on outcome of intravesical instillation of bacillus Calmette-Guerin immunotherapy for bladder cancer.2006

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      Clin.Cancer Res. 12

      Pages: 4641-4644

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus Calmette-Guerin immunotherapy for bladder cancer.2006

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      Clin. Cancer Res. 12

      Pages: 4641-4644

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer : implications for specific immunotherapy.2006

    • Author(s)
      Kitamura, H. et al.
    • Journal Title

      Urology 67

      Pages: 955-959

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Induction of autologous CD4- and CD8-mediated T-cell responses against acute lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells.2006

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

      Exp.Hematol. 34

      Pages: 197-207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Survivin expression is regulated by coexpression of Human Epidermal Growth Factor Receptor 2 and Epidermal Growth Factor Receptor via Phosphatidylinositol 3-Kinase/AKT signaling pathway in breast cancer cells.2005

    • Author(s)
      Asanuma, H.
    • Journal Title

      Cancer Research 65

      Pages: 11018-11025

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis.2005

    • Author(s)
      Yamamoto, M.
    • Journal Title

      Cancer Research 65

      Pages: 8706-8714

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A quest for therapeutic antigens in bone and soft tissue sarcoma.2005

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

      J.Translational Medicine 3

      Pages: 31-38

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in Lung Cancer.2005

    • Author(s)
      Hariu, H.
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 1000-1009

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptotis proteins.2005

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

      Clin.Cancer Res. 11

      Pages: 1474-1482

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant expression and potency as a cancer immunotherapy target of IAP family, Livin/ML-IAP in Lung Cancer.2005

    • Author(s)
      Hariu, H.
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 1000-1009

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of human autologous cytotoxic T-lymphocyte-defined osteosarcoma gene that encodes a transcriptional regulator, papillomavirus binding factor.2004

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

      Cancer Res. 64

      Pages: 5442-5448

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tumor-derived heat shock protein70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymophocytes (CTLs) and tumor immunity.2004

    • Author(s)
      Ueda, G.
    • Journal Title

      Cancer Science 95

      Pages: 248-253

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer.2004

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

      J.Translational Med. 2

      Pages: 19-29

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A^*2402 anchor substitute.2004

    • Author(s)
      Ida, K.
    • Journal Title

      J.Immunol. 173

      Pages: 1436-1443

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of MHC class II expression in glioma cells by class II transactivator (C IITA).2004

    • Author(s)
      Takamura, Y.
    • Journal Title

      Glia 45

      Pages: 392-405

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition of endogenous MHC class II-restricted minor histocompatibility antigen presentation by tacrolimus(FK506) via FKBP51.

    • Author(s)
      Imai, A. et al.
    • Journal Title

      Eur.J.Immunol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Book] Heat Shock Proteins in Biology and Medicine2006

    • Author(s)
      Tamura, Y. et al.
    • Publisher
      Extracellular heat shock proteins in immune response : A euide for cross-presentation.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Heat Shock Proteins in Biology and Medicine2006

    • Author(s)
      Tamura, Y. et al.
    • Publisher
      Extracellular heat shock proteins in immune response : A guide for cross-presentation.
    • Related Report
      2006 Annual Research Report
  • [Book] Annual Review 免疫2006

    • Author(s)
      大浦 淳, 佐藤昇志, 他
    • Total Pages
      6
    • Publisher
      中外医学社
    • Related Report
      2005 Annual Research Report
  • [Book] Annual Review免疫2005;熱ショック蛋白質(HSP)-ペプチド複合体による新しいMHCクラスI抗原提示経路(佐藤昇志, 他編集)2005

    • Author(s)
      田村保明, 佐藤昇志
    • Total Pages
      8
    • Publisher
      中外医学社
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 変性ヒト癌抗原に特異的なマウスモノクローナル抗体2006

    • Inventor(s)
      佐藤昇志他
    • Industrial Property Rights Holder
      佐藤昇志他
    • Industrial Property Number
      2006-260696
    • Filing Date
      2006-09-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 変性HLAへclass I重鎖を認識するマウス単クローン抗体2005

    • Inventor(s)
      佐藤 昇志, 鳥越 俊彦, 下澤 久美子, 中澤 恵実理
    • Industrial Property Rights Holder
      佐藤 昇志, 鳥越 俊彦, 下澤 久美子, 中澤 恵実理
    • Industrial Property Number
      2005-094920
    • Filing Date
      2005-03-29
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] サバイビン由来HLA-A24結合性癌抗原ペプチド2004

    • Inventor(s)
      佐藤 昇志他4名
    • Industrial Property Rights Holder
      佐藤 昇志他4名
    • Industrial Property Number
      2004-191478
    • Filing Date
      2004-01-30
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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