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Immunological analysis of treatment resistant cancer stem cells

Research Project

Project/Area Number 24590449
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

HIROHASHI Yoshihiko  札幌医科大学, 医学部, 講師 (30516901)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsがん幹細胞 / 免疫療法 / がん抗原 / がん精巣抗原 / DNAJB8 / OR7C1 / 大腸がん / 腫瘍抗原 / 抗原分子
Outline of Final Research Achievements

In this research period, we isolated cancer stem-like cells(CSCs)/cancer-initiating cells(CICs) from human lung, colon and kidney cancer line cells. To identify CSC/CIC-specific genes, we performed cDNA microarray analysis and found that numbers of cancer-testis (CT) antigens including OR7C1, DNAJB8 and SMCP were preferentially expressed in CSCs/CICs. Furthremore, we identified HLA-A24 restricted antigenic peptides encoded by amino acid sequences of OR7C1 and DNAJB8. Cytotoxic T lymphocytes (CTLs) specific for OR7C1 peptide and DNAJB8 peptide showed preferential cytotoxicity for CSCs/CICs compared with that of non-CSCs/CICs. These observations indicate that CT antigens-specific cancer immunotherapy might be promising approach for targeting treatment resistant CSCs/CICs.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (23 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 3 results,  Acknowledgement Compliant: 5 results) Presentation (10 results) (of which Invited: 9 results)

  • [Journal Article] Expression of hepatocyte growth factor in prostate cancer may indicate a biochemical recurrence after radical prostatectomy.2015

    • Author(s)
      Nishida S, Hirohashi Y, Torigoe T, Nojima M, Inoue R, Kitamura H, Tanaka T, Asanuma H, Sato N, Masumori N.
    • Journal Title

      Anticancer Res

      Volume: 35 Pages: 413-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells.2014

    • Author(s)
      Morita R, Nishizawa S, Torigoe T, Takahashi A, Tamura Y, Tsukahara T, Kanaseki T, Sokolovskaya A, Kochin V, Kondo T, Hashino S, Asaka M, Hara I, Hirohashi Y, Sato N.
    • Journal Title

      Cancer Sci

      Volume: 105 Issue: 4 Pages: 389-395

    • DOI

      10.1111/cas.12362

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Production of multiple CTL epitopes from multiple tumor-associated antigens.2014

    • Author(s)
      Morita R, Hirohashi Y, Nakatsugawa M, Kanaseki T, Torigoe T, Sato N.
    • Journal Title

      Methods Mol Biol

      Volume: 1139 Pages: 345-55

    • DOI

      10.1007/978-1-4939-0345-0_28

    • ISBN
      9781493903443, 9781493903450
    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Prognostic impact of human leukocyte antigen class I expression and association of platinum resistance with immunologic profiles in epithelial ovarian cancer.2014

    • Author(s)
      Mariya T, Hirohashi Y, Torigoe T, Asano T, Kuroda T, Yasuda K, Mizuuchi M, Sonoda T, Saito T, Sato N.
    • Journal Title

      Cancer Immunol Res

      Volume: 2 Issue: 12 Pages: 1220-9

    • DOI

      10.1158/2326-6066.cir-14-0101

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity.2014

    • Author(s)
      Yasuda K, Torigoe T, Mariya T, Asano T, Kuroda T, Matsuzaki J, Ikeda K, Yamauchi M, Emori M, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato N.
    • Journal Title

      Lab Invest

      Volume: 94 Issue: 12 Pages: 1355-69

    • DOI

      10.1038/labinvest.2014.122

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ectopically expressed variant form of sperm mitochondria-associated cysteine-rich protein augments tumorigenicity of the stem cell population of lung adenocarcinoma cells.2013

    • Author(s)
      Takahashi A, Hirohashi Y, Torigoe T, Tamura Y, Tsukahara T, Kanaseki T, Kochin V, Saijo H, Kubo T, Nakatsugawa M, Asanuma H, Hasegawa T, Kondo T, Sato N.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 11 Pages: e69095-e69095

    • DOI

      10.1371/journal.pone.0069095

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.2013

    • Author(s)
      Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato N.
    • Journal Title

      PLoS One

      Volume: 8(8) Issue: 8 Pages: e68187-e68187

    • DOI

      10.1371/journal.pone.0068187

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal.2013

    • Author(s)
      Michifuri Y, Hirohashi Y, Torigoe T, Miyazaki A, Fujino J, Tamura Y, Tsukahara T, Kanaseki T, Kobayashi J, Sasaki T, Takahashi A, Nakamori K, Yamaguchi A, Hiratsuka H, Sato N.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 439 Issue: 1 Pages: 96-102

    • DOI

      10.1016/j.bbrc.2013.08.021

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preferential expression of cancer/testis genes in cancer stem-like cells : proposal of a novel sub-category, cancer/testis/stem gene.2013

    • Author(s)
      Yamada R, Takahashi A, Torigoe T, Morita R, Tamura Y, Tsukahara T, Kanaseki T, Kubo T, Watarai K, Kondo T, Hirohashi Y, Sato N.
    • Journal Title

      Tissue Antigens.

      Volume: 81(6) Issue: 6 Pages: 428-34

    • DOI

      10.1111/tan.12113

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor.2013

    • Author(s)
      Nishida S, Hirohashi Y, Torigoe T, Inoue R, Kitamura H, Tanaka T, Takahashi A, Asanuma H, Masumori N, Tsukamoto T, Sato N.
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 4 Pages: 431-6

    • DOI

      10.1111/cas.12104

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression and function of FERMT genes in colon carcinoma cells2013

    • Author(s)
      Kiriyama K, Hirohashi Y, Torigoe T, et al.
    • Journal Title

      Anticancer Res

      Volume: 33 Pages: 167-73

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA methyltransferase 1 is essential for initiation of the colon cancers2013

    • Author(s)
      Morita R,Hirohashi Y,Suzuki H, et al
    • Journal Title

      Experimental and Molecular Pathology

      Volume: 94 Issue: 2 Pages: 322-329

    • DOI

      10.1016/j.yexmp.2012.10.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Depletion of Tregs in vivo: a promising approach to enhance antitumor immunity without autoimmunity2012

    • Author(s)
      Morita R,Hirohashi Y,Sato N.
    • Journal Title

      Immunotherapy

      Volume: 4 Issue: 11 Pages: 1103-1105

    • DOI

      10.2217/imt.12.116

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトがん幹細胞免疫制御の分子病理学的基盤2014

    • Author(s)
      廣橋良彦
    • Organizer
      第60回日本病理学会秋季特別総会
    • Place of Presentation
      国立劇場おきなわ(沖縄県・浦添市)
    • Year and Date
      2014-11-19 – 2014-11-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 6.Cytotoxic T lymphocytes play a key role in immunological responses to human cancer stem-like cells2014

    • Author(s)
      廣橋良彦
    • Organizer
      第33回 札幌がんセミナー国際シンポジウム
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Year and Date
      2014-06-28 – 2014-06-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がん幹細胞を標的とする免疫療法の基礎的検討2013

    • Author(s)
      廣橋良彦、鳥越俊彦、守田玲菜、西澤 哲、井野田智子、髙橋あかり、佐藤昇志
    • Organizer
      第17回日本がん免疫学会総会
    • Place of Presentation
      宇部市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] がん幹細胞におけるストレス応答遺伝子の活性化とその意義2013

    • Author(s)
      廣橋良彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] A novel cancer-initiating cell marker, OR7C1 can be a target of immunotherapy2013

    • Author(s)
      Yoshihiko Hirohashi, Toshihiko Torigoe, Rena Morita, Satoshi Nishizawa, Satoko Inoda, Akari Takahashi and Noriyuki Sato
    • Organizer
      第72回日本がん学会総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] 腎臓癌の幹細胞と治療戦略2013

    • Author(s)
      廣橋良彦
    • Organizer
      第6回 Tokyo Metropolitan Kidney Cancer Meeting
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 新規HSP40ファミリーDNAJB8はがん幹細胞の維持に関わり、免疫療法の標的となりうる2013

    • Author(s)
      廣橋良彦、鳥越俊彦、西澤 哲、原 勲、佐藤昇志
    • Organizer
      日本ハイパーサーミア学会第30回大会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 熱ショックによりがん抗原特異的細胞傷害活性T細胞機能が亢進する2013

    • Author(s)
      廣橋良彦、鳥越俊彦、髙橋あかり、佐藤昇志
    • Organizer
      第29回日本ストレス学会総会
    • Place of Presentation
      徳島市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Cancer Immunotherapy targeting to cancer stem cell/cancer initiating cell

    • Author(s)
      廣橋良彦
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] がん幹細胞標的ペプチドワクチン

    • Author(s)
      廣橋良彦
    • Organizer
      第10回日本臨床腫瘍学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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