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Mechanisms of tumor-induced immune tolerance during the process of peritoneal dissemination of ovarian cancer

Research Project

Project/Area Number 23592459
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionWakayama Medical University

Principal Investigator

INO Kazuhiko  和歌山県立医科大学, 医学部, 教授 (60303640)

Co-Investigator(Kenkyū-buntansha) MABUCHI Yasushi  和歌山県立医科大学, 医学部, 助教 (80382357)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords卵巣癌 / 腫瘍免疫 / 免疫寛容 / 腹膜播種 / マウスモデル / 酵素 / 卵巣がん / 免疫療法
Research Abstract

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. IDO-cDNA was transfected into the murine ovarian carcinoma cell line HM-1, establishing IDO-overexpressing cells (HM-1-IDO). HM-1-IDO or mock were intraperitoneally transplanted into syngeneic immunocompetent mice. HM-1-IDO-transplanted mice showed significantly shortened survival, and increased tumor weight and ascites with the significantly reduced numbers of CD8+ T cells and NK cells within tumors as well as increased levels of TGF-beta in ascites. These data show that tumoral IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating T and NK-cell recruitment and enhancement of immunosuppressive cytokines in ascites, thus IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012 2011

All Journal Article (12 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (8 results) (of which Invited: 2 results)

  • [Journal Article] Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.2014

    • Author(s)
      Tanizaki Y(1), Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 8 Pages: 966-73

    • DOI

      10.1111/cas.12445

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer2014

    • Author(s)
      Tanizaki Y, Kobayashi A, Shiro M, Ota N, Takano R, Mabuchi Y, Yagi S, Minami S, Terada M, Ino K
    • Journal Title

      Int J Gynecol Cancer

      Volume: 24(3) Issue: 3 Pages: 454-60

    • DOI

      10.1097/igc.0000000000000074

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix : a case study2013

    • Author(s)
      Yasuoka H, Tsujimoto M, Ueda M, Kodama R, Iwahashi Y, Inagaki M, Mabuchi Y, Ino K, Sanke T, Nakamura Y
    • Journal Title

      Int J Gynecol Pathol

      Volume: 32(4) Issue: 4 Pages: 416-20

    • DOI

      10.1097/pgp.0b013e318261c35b

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role of the immune tolerance-inducing molecule indoleamine 2,3-dioxygenase in gynecologic cancers2013

    • Author(s)
      Ino K, Tanizaki Y, Kobayashi A, et al.
    • Journal Title

      J Cancer Sci Ther

      Volume: 4(S13) Pages: 1-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.2013

    • Author(s)
      Niimi K, Yamamoto E, Fujiwara S, Shinjo K, Kotani T, Umezu T, Kajiyama H, Shibata K, Ino K, Kikkawa F.
    • Journal Title

      Br J Cancer

      Volume: 107 Issue: 12 Pages: 1969-1977

    • DOI

      10.1038/bjc.2012.496

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma2012

    • Author(s)
      Yasuoka H, Tsujimoto M, Inagaki M, Kodama R, Tsuji H, Iwahashi Y, Mabuchi Y, Ino K, Sanke T, Nakamura Y
    • Journal Title

      J Clin Pathol

      Volume: 65(5) Issue: 5 Pages: 399-402

    • DOI

      10.1136/jclinpath-2011-200359

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of the immune tolerance-inducing molecule indoleamine 2,3-dioxygenase in gynecologic cancers2012

    • Author(s)
      Ino K, Tanizaki Y, Kobayashi A, Toujima S, Mabuchi Y, Minami S
    • Journal Title

      Journal of Cancer Science & Therapy

      Volume: 4(S13) Pages: 1-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spectrin αII and βII tetramers contribute to platinum anticancer drug resistance in ovarian serous adenocarcinoma2012

    • Author(s)
      Maeda O, Kajiyama H, 他
    • Journal Title

      Int J Cancer

      Volume: 130 Issue: 1 Pages: 113-121

    • DOI

      10.1002/ijc.25983

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the immune tolerance-inducing molecule IDO in gynecologic cancers.2012

    • Author(s)
      Ino K, Tanizaki Y, Kobayashi A, et al.
    • Journal Title

      Journal of Cancer Science and Therapy

      Volume: in press

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the renin-angiotensin system in gynecologic cancers2011

    • Author(s)
      Ino K, Shibata K, Yamamoto E, Kajiyama H, Nawa A, Mabuchi Y, Yagi S, Minami S, Tanizaki Y, Kobayashi A, Kikkawa F
    • Journal Title

      Curr Cancer Drug Targets

      Volume: 11(4):. Pages: 405-11

    • Related Report
      2013 Final Research Report
  • [Journal Article] Indoleamine 2,3-dioxygenase and immune tolerance in ovarian cancer2011

    • Author(s)
      Ino K
    • Journal Title

      Curr Opin Obstet Gynecol

      Volume: 23(1) Issue: 1 Pages: 13-8

    • DOI

      10.1097/gco.0b013e3283409c79

    • Related Report
      2013 Final Research Report
  • [Journal Article] IDO and immune tolerance in ovarian cancer2011

    • Author(s)
      Ino K
    • Journal Title

      Current Opinion Obstetrics and Gynecology

      Volume: 23 Pages: 13-18

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Suppression of STAT1 signal pathways reduces ovarian cancer progression2013

    • Author(s)
      Aya Kobayashi, Yuko Tanizaki, Saori Toujima, Tamaki Yahata, Madoka Yamamoto, Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Toshikazu Kondo, Kazuhiko Ino
    • Organizer
      The 3rd ASGO / The 55th JSGO
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Final Research Report
  • [Presentation] Pivotal roles of CX3CL1-CX3CR1 axis on host cells in ovarian cancer progression2013

    • Author(s)
      Yuko Tanizaki, Aya Kobayashi, Saori Toujima, Tamaki Yahata, Madoka Yamamoto, Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka Yagi, Sawako Minami, Toshikazu Kondo, Kazuhiko Ino
    • Organizer
      The 3rd ASGO / The 55th JSGO
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Final Research Report
  • [Presentation] Essential involvement of tumor-derived IDO in ovarian cancer progression2013

    • Author(s)
      Tanizaki Y, Kobayashi A, Ino K et al.
    • Organizer
      15th International Congress of Immunology 2013
    • Place of Presentation
      イタリア ミラノ
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Suppression of STAT1 signal pathways reduces ovarian cancer progression2013

    • Author(s)
      Kobayashi A, Tanizaki Y, Ino K, et al
    • Organizer
      3rd Meeting of Asia Society of Gynecologic Oncology
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 免疫寛容を誘導するIndoleamine 2,3-dioxygenaseは卵巣癌腹膜播種を促進し、新規標的治療の候補分子になり得る2012

    • Author(s)
      谷﨑優子、小林彩、東嶋左緒里、山本円、馬淵泰士、八木重孝、岩橋正明、南佐和子、井箟一彦
    • Organizer
      第11回婦人科がん分子標的研究会
    • Place of Presentation
      日光.
    • Related Report
      2013 Final Research Report
  • [Presentation] 免疫寛容誘導分子IDOは卵巣癌腹膜播種を促進する2012

    • Author(s)
      谷崎優子、小林彩、山本円、馬淵泰士、岩橋正明、南佐和子、井箟一彦
    • Organizer
      第64回日本産科婦人科学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] 免疫寛容分子IDOは卵巣癌腹膜播種を促進する2012

    • Author(s)
      谷﨑優子、小林彩、山本円、馬淵泰士、岩橋正明、南佐和子、井箟一彦
    • Organizer
      第64回日本産科婦人科学会学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] 免疫寛容を誘導するIndoleamine 2,3-dioxygenaseは卵巣癌腹膜播種を促進し、新規標的治療の候補分子になり得る2012

    • Author(s)
      谷﨑優子、小林彩、東嶋左緒里、山本円、馬淵泰士、八木重孝、岩橋正明、南佐和子、井箟一彦
    • Organizer
      第11回婦人科がん分子標的研究会学術集会
    • Place of Presentation
      日光
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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