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2006 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 2004 – 2006
Keywordscancer vaccine / survivin / SYT-SSX / HLA class I down regulation / immune escape / epigenetics / HAD inhibitor / HSP90
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.

  • Research Products

    (13 results)

All 2007 2006

All Journal Article (11 results) Book (1 results) Patent(Industrial Property Rights) (1 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [Book] Heat Shock Proteins in Biology and Medicine2006

    • Author(s)
      Tamura, Y. et al.
    • Total Pages
      119-130
    • 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
  • [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
      特願2006-260696
    • Filing Date
      2006-09-26
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2008-05-27  

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