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Analyses of tumor heterogeneity and peritoneal tumor microenvironment in ovarian cancer for development of novel tumor immunotherapy

Research Project

Project/Area Number 15K20138
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionNagoya University

Principal Investigator

SUZUKI Shiro  名古屋大学, 医学部附属病院, 講師 (20612758)

Research Collaborator NAKATSURA Tetsuya  国立がん研究センター, 先端医療開発センター, 免疫療法開発分野長
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords卵巣がん / 腹膜播種
Outline of Final Research Achievements

We established a subclone of ID8 mouse ovarian cancer cell line (ID8-T6) which more quickly forms peritoneal dissemination. IL-33 was up-regulated in both ID8-T6 cells and tissue compared with for ID8. We confirmed the expression of IL-33 in human epithelial ovarian cancer (EOC) cell lines. Unexpectedly, the survival rate of IL33-overexpressing subclone (ID8-IL33) tumor-bearing mice was significantly prolonged compared with that of ID8-mock tumor-bearing mice. Infiltrating CD4+ cells and CD8+ cells within the disseminated tumor tissues were significantly increased in ID8-IL33 tumors compared with in ID8-mock tumors. In contrast, myeloid-derived suppressor cells (MDSCs) were significantly decreased in IL33-overexpressing tumors. Ascites from ID8-IL33 tumor-bearing mice inhibited MDSC differentiation. EOC patients with high staining of IL-33 had significantly longer overall survival times.
We also established ID8 chemo-resistant subclones and heterogeneity assessment mouse models.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (20 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The possible existence of occult metastasis in patients with ovarian clear-cell carcinoma who underwent complete resection without any residual tumours2018

    • Author(s)
      Kajiyama Hiroaki、Suzuki Shiro、Yoshihara Masato、Nishino Kimihiro、Yoshikawa Nobuhisa、Utsumi Fumi、Niimi Kaoru、Mizuno Mika、Kawai Michiyasu、Oguchi Hidenori、Mizuno Kimio、Yamamuro Osamu、Nagasaka Tetsuro、Shibata Kiyosumi、Kikkawa Fumitaka
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 5 Pages: 6298-6307

    • DOI

      10.18632/oncotarget.23921

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of ZEB1 leads to inversion of metastatic characteristics and restoration of paclitaxel sensitivity of chronic chemoresistant ovarian carcinoma cells2017

    • Author(s)
      Sakata Jun、Utsumi Fumi、Suzuki Shiro、Niimi Kaoru、Yamamoto Eiko、Shibata Kiyosumi、Senga Takeshi、Kikkawa Fumitaka、Kajiyama Hiroaki
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 59 Pages: 99482-99494

    • DOI

      10.18632/oncotarget.20107

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel mechanism of neovascularization in peritoneal dissemination via cancer-associated mesothelial cells affected by TGF-β derived from ovarian cancer2017

    • Author(s)
      Fujikake Kayo、Kajiyama Hiroaki、Yoshihara Masato、Nishino Kimihiro、Yoshikawa Nobuhisa、Utsumi Fumi、Suzuki Shiro、Niimi Kaoru、Sakata Jun、Mitsui Hiroko、Shibata Kiyosumi、Senga Takeshi、Kikkawa Fumitaka
    • Journal Title

      Oncology Reports

      Volume: 39 Pages: 193-200

    • DOI

      10.3892/or.2017.6104

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of positive ZEB1 expression in patients with epithelial ovarian carcinoma as an oncologic outcome-predicting indicator2017

    • Author(s)
      Sakata Jun、Kajiyama Hiroaki、Suzuki Shiro、Utsumi Fumi、Niimi Kaoru、Sekiya Ryuichiro、Shibata Kiyosumi、Senga Takeshi、Kikkawa Fumitaka
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 4 Pages: 4287-4293

    • DOI

      10.3892/ol.2017.6658

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance and predicting indicators of post-cancer-treatment survival in terminally ill patients with ovarian cancer.2017

    • Author(s)
      Utsumi F, Kajiyama H, Niimi K, Sekiya R, Sakata J, Suzuki S, Shibata K, Mizuno M, Kikkawa F.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 43 Issue: 2 Pages: 365-370

    • DOI

      10.1111/jog.13219

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma.2016

    • Author(s)
      Suzuki S, Sakata J, Utsumi F, Sekiya R, Kajiyama H, Shibata K, Kikkawa F, Nakatsura T.
    • Journal Title

      Oncoimmunology

      Volume: 5 Issue: 11 Pages: e1238542-e1238542

    • DOI

      10.1080/2162402x.2016.1238542

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells.2016

    • Author(s)
      Yoshikawa N, Kajiyama H, Nakamura K, Utsumi F, Niimi K, Mitsui H, Sekiya R, Suzuki S, Shibata K, Callen D, Kikkawa F.
    • Journal Title

      Oncol Rep

      Volume: 35(5) Issue: 5 Pages: 2543-52

    • DOI

      10.3892/or.2016.4653

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs.2015

    • Author(s)
      Yamada E, Demachi-Okamura A, Kondo S, Akatsuka Y, Suzuki S, Shibata K, Kikkawa F, Kuzushima K.
    • Journal Title

      Tissue Antigens

      Volume: 86(3) Issue: 3 Pages: 164-71

    • DOI

      10.1111/tan.12607

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] The prognostic impact of pulmonary metastasectomy in recurrent gynecologic cancers: a retrospective single-institution study.2015

    • Author(s)
      Adachi M, Mizuno M, Mitsui H, Kajiyama H, Suzuki S, Sekiya R, Utsumi F, Shibata K, Taniguchi T, Kawaguchi K, Yokoi K, Kikkawa F.
    • Journal Title

      Nagoya J Med Sci

      Volume: 77(3) Pages: 363-72

    • NAID

      120005649103

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Opioid needs of terminally ill patients with gynecologic malignancies.2015

    • Author(s)
      Utsumi F, Kajiyama H, Sakata J, Higashi M, Niimi K, Sekiya R, Mitsui H, Suzuki S, Umezu T, Mizuno M, Yamamoto E, Shibata K, Kikkawa F
    • Journal Title

      Int J Clin Oncol.

      Volume: 20 Issue: 2 Pages: 405-10

    • DOI

      10.1007/s10147-014-0708-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 卵巣癌におけるIL-33に着目した腹腔内免疫環境の基礎的・臨床的研究2018

    • Author(s)
      関谷 敦史, 鈴木 史朗, 清水 裕介, 芳川 修久, 坂田 純, 内海 史, 梶山 広明, 吉川 史隆
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 婦人科がんにおける個別化免疫療法の開発2018

    • Author(s)
      野坂 和外, 吉川 聡明, 鈴木 利宙, 齋藤 桂吾, 下村 真菜美, 水野 正一, 鈴木 史朗, 吉川 史隆, 中面 哲也
    • Organizer
      第15回日本免疫治療学研究会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ESTABLISHMENT AND CHARACTERISATION OF PATIENT-DERIVED XENOGRAFT MODELS FOR MALIGNANT GYNECOLOGIC TUMORS2017

    • Author(s)
      鈴木 史朗, 玉内 学志, 清水 裕介, 吉原 雅人, 中村 謙一, 芳川 修久, 梶山 広明, 吉川 史隆
    • Organizer
      20th Biennial Meeting of the European Society of Gynaecological Oncology (ESGO 2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗癌剤耐性再発卵巣癌における耐性能の可逆性とDrug-rechallengeへの応答2017

    • Author(s)
      坂田 純, 梶山 広明, 内海 史, 新美 薫, 関谷 龍一郎, 鈴木 史朗, 柴田 清住, 吉川 史隆
    • Organizer
      第59回日本婦人科腫瘍学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 婦人科がんpatient-derived xenograftモデルの構築2017

    • Author(s)
      鈴木 史朗, 坂田 純, 内海 史, 関谷 龍一郎, 梶山 広明, 柴田 清住, 吉川 史隆
    • Organizer
      第69回日本産科婦人科学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 卵巣明細胞腺癌に対するGPC3を標的としたペプチドワクチン療法 ~臨床第Ⅱ相試験のデータ解析から見える今後の課題~2016

    • Author(s)
      鈴木 史朗, 柴田 清住, 吉川 史隆, 中面 哲也
    • Organizer
      第20回日本がん免疫学会総会
    • Place of Presentation
      大阪国際交流センター(大阪府大阪市天王寺区)
    • Year and Date
      2016-07-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 卵巣癌における新規腫瘍抗原KIF20A発現の検討とペプチドカクテルワクチン療法への臨床応用2016

    • Author(s)
      河合要介, 鈴木史朗, 梶山広明, 柴田清住, 吉川史隆
    • Organizer
      第20回日本がん免疫学会総会
    • Place of Presentation
      大阪国際交流センター(大阪府大阪市天王寺区)
    • Year and Date
      2016-07-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗癌剤耐性ヒト卵巣癌細胞株における5-アミノレブリン酸を用いた光線力学療法の検討2016

    • Author(s)
      勅使河原 利哉, 水野 美香, 石井 琢也, 三井 寛子, 内海 史, 関谷 龍一郎, 鈴木 史朗, 梶山 広明, 柴田 清住, 高橋 究, 石塚 昌宏, 吉川 史隆
    • Organizer
      第58回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2016-07-08
    • Related Report
      2016 Research-status Report
  • [Presentation] A biomarker analysis in a clinical study of the GPC3 peptide vaccine for patients with ovarian clear cell carcinoma2015

    • Author(s)
      鈴木史朗, 柴田清住, 吉川史隆, 中面哲也
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] ミニワークショップ5:卵巣明細胞腺癌患者におけるHLA-Aアリル多型性の検討2015

    • Author(s)
      鈴木史朗, 内海史, 三井寛子, 関谷龍一郎, 梶山広明, 柴田清住, 吉川史隆
    • Organizer
      第57回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      いわて県民情報交流センター(岩手県盛岡市)
    • Year and Date
      2015-08-07
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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