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immune environment in the peritoneal cavity and development of novel immune therapy in ovarian cancer

Research Project

Project/Area Number 21592130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

MANDAI Masaki  京都大学, 医学研究科, 講師 (80283597)

Co-Investigator(Kenkyū-buntansha) KONISHI Ikuo  京都大学, 医学研究科, 教授 (90192062)
MATSUMURA Noriomi  京都大学, 医学研究科, 助教 (20452336)
八木 治彦  京都大学, 医学研究科, 助教 (70402857)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords卵巣癌 / 腹膜播種 / 腫瘍免疫 / PD-L1 / 免疫逃避機構 / 局所免疫 / 包括的解析 / 予後 / 局所免疫環境 / 化学療法 / CD8T細胞 / 腹腔内進展
Research Abstract

In this study, we hypothesized that cancer cells actively alter immune environment in the peritoneal cavity I order to disseminate. By using human ovarian cancer samples as well as mouse ovarian cancer peritoneal dissemination model, we thoroughly analyzed the association between immune environment and cancer dissemination. We found that PD-L1, an immune suppressive molecule, is expressed or induced by encountering the immune cells in the peritoneal cavity. Forced expression of PD-L1 resulted in the promotion of peritoneal dissemination, while inhibition of PD-L1 inhibited it. These result indicate that, in ovarian cancers with high PD-L1 expression, this molecule could be a therapeutic target to suppress peritoneal dissemination.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (25 results)

All 2012 2011 2010 2009

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (9 results)

  • [Journal Article] 卵巣癌の播種・進展と免疫環境との関連分子を標的とした治療法の開発2012

    • Author(s)
      万代昌紀、濱西潤三、安彦郁、松村謙臣、馬場長、小阪謙三、吉岡弓子、小西郁生
    • Journal Title

      産婦人科の実際

      Volume: 61 Pages: 201-205

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer2012

    • Author(s)
      Yamamura S, Matsumura N, Mandai M, Huang Z, Oura T, Baba T, Hamanishi J, Yamaguchi K, Kang HS, Okamoto T, Abiko K, Mori S, Murphy SK, Konishi I.
    • Journal Title

      Int J Cancer

      Volume: 130(1) Issue: 1 Pages: 20-8

    • DOI

      10.1002/ijc.25961

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian2012

    • Author(s)
      Yamamura S, Matsumura N, Mandai M, et al
    • Journal Title

      Int J Cancer

      Volume: 130 Pages: 20-28

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors2011

    • Author(s)
      Hamanishi J, Mandai M, Abiko K, Matsumura N, Baba T, Yoshioka Y, Kosaka K, Konishi I
    • Journal Title

      Clin Immunol

      Volume: 141(3) Pages: 338-47

    • NAID

      120003610113

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ovarian clear cell carcinoma as a stress-responsive cancer2011

    • Author(s)
      Mandai M, Matsumura N, et al
    • Journal Title

      Cancer Lett

      Volume: 310 Pages: 129-133

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors2011

    • Author(s)
      Hamanishi J, Mandai M, et al
    • Journal Title

      Clin Immunol

      Volume: 141 Pages: 338-347

    • NAID

      120003610113

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian cancer2010

    • Author(s)
      Hamanishi J, Mandai M, Matsumura N, Baba T, Yamaguchi K, Fujii S, Konishi I
    • Journal Title

      Stem Cells

      Volume: 28(1) Pages: 164-73

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated local immunity by CC chemokine ligand 19-transduced embryonic endothelial progenitor cells suppresses metastasis of murine ovarian2010

    • Author(s)
      Hamanishi J, Mandai M, et al
    • Journal Title

      Stem Cells

      Volume: 28 Pages: 164-173

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes2010

    • Author(s)
      Yamaguchi K, Mandai M, et al
    • Journal Title

      Oncogene

      Volume: 29 Pages: 1741-1752

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actived local immunity by CC chemokine ligand 19-transduced embry onic endothelial progenitor cells suppresses metastasis of murine ovarian cancer.2010

    • Author(s)
      Hamanishi J, Mandai M, Matsumura N, et al.
    • Journal Title

      Stem Cells

      Volume: 28(1) Pages: 164-73

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes.2010

    • Author(s)
      Yamaguchi K, Mandai M, Oura T, et al.
    • Journal Title

      Oncogene

      Volume: 29(12) Pages: 1741-52

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Minimal deviation mucinous adenocarcinoma ('adenoma malignum') of the uterine corpus.2010

    • Author(s)
      Abiko K, Baba T, Koyama T, Mandai M, et al.
    • Journal Title

      Pathol Int

      Volume: 60(1) Pages: 42-7

    • NAID

      10027382724

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oct4 expression in immature teratoma of the ovary : relevance to histologic grade and degree of differentiation.2010

    • Author(s)
      Abiko K, Mandai M, Hamanishi J, et al.
    • Journal Title

      Am J Surg Pathol

      Volume: 34(12) Pages: 1842-48

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sorafenib efficacy in ovarian clear cell carcinoma revealed by transcriptome profiling.2010

    • Author(s)
      Matsumura N, Mandai M, Okamoto T, et al.
    • Journal Title

      Cancer Sci

      Volume: 101(12) Pages: 2658-63

    • NAID

      10027834982

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of an Ovarian Clear Cell Carcinoma Gene Signature that reflects inherent disease biology and the carcinogenic processes.2010

    • Author(s)
      Yamaguchi K, Mandai M, et al
    • Journal Title

      Oncogene 29

      Pages: 1741-1752

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated local immunity by CC chemokine ligand 19-transduced embry onic endothelial progenitor cells suppresses metastasis of murine ovarian cancer.2010

    • Author(s)
      Hamanishi J, Mandai M, et al
    • Journal Title

      Stem Cells 28

      Pages: 164-173

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 免疫抑制因子PD-L1は卵巣癌の免疫逃避機構を介して腹膜播種を促進する2012

    • Author(s)
      安彦郁、万代昌紀、濱西潤三、吉岡弓子、馬場長、松村謙臣、山口建、Budiman Kharma、奈倉道和、天野泰彰、小阪謙三、小西郁生
    • Organizer
      日本産科婦人科学会
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] Assessment and manipulation of local tumor immunity in ovarian cancer management2011

    • Author(s)
      Masaki Mandai, Junzo Hamanishi, Kaoru Abiko, Noriomi Matsumura, Tsukasa Baba, Ken Yamaguchi, Kenzo Kosaka, Ikuo Konishi
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] 進行卵巣癌に対する化学療法によって、腫瘍局所の免疫状態が変化する2011

    • Author(s)
      濱西潤三、万代昌紀、安彦郁、松村謙臣、馬場長、山村省吾、吉岡弓子、岡本尊子、姜賢淑、奈倉道和、小阪謙三、小西郁生
    • Organizer
      日本産科婦人科学会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] 卵巣癌における局所免疫環境の評価と治療への応用2011

    • Author(s)
      万代昌紀、浜西潤三, 他
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Annual Research Report
  • [Presentation] Microarray-based ovarian clear cell carcinoma signature predicts sorafenib as a promising reagent targeting specific cell signaling2010

    • Author(s)
      Mandai M, Yamaguchi K, Matsumura N, et al.
    • Organizer
      IGCS2010 (13th Biennial Meeting of the International Gynecologic Cancer Society)
    • Place of Presentation
      Prague Congress centre, Czech Republic
    • Year and Date
      2010-10-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Suppression of metastatic murine ovarian cancer cells by transduced embryonic progenitor cells2010

    • Author(s)
      Mandai M, Hamanishi J, Matsumura N, Baba T, Konishi I
    • Organizer
      The 6th International Symposium on Hormonal Oncogenesis
    • Place of Presentation
      シェラトングランデベイホテル(千葉)(招待講演)
    • Year and Date
      2010-09-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血管内皮前駆細胞を用いた新規がん免疫療法の基礎的検討2010

    • Author(s)
      濱西潤三、万代昌紀、松村謙臣, 他
    • Organizer
      第51回日本組織細胞化学会学術集会ワークショップ「癌研究の最近のトピックス」
    • Place of Presentation
      東京 秋葉原コンベンションホール
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] The immunlolgic change in advanced ovarian cancer patients after chemotherapy with paclitaxel or carboplatin2010

    • Author(s)
      Hamanishi J, Mandai M, Konishi I.
    • Organizer
      14th International congress of Immunology(第14回国際免疫学会議)
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2010 Annual Research Report
  • [Presentation] 卵巣癌局所における免疫環境を推測する新たな解析法とその意義2009

    • Author(s)
      濱西潤三、万代昌紀, 他
    • Organizer
      日本婦人科がん分子標的研究会
    • Place of Presentation
      福岡市
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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