• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Clinical utilization and investigation of ovarian cancer genome diversity associated with metastasis, resistance to treatment and immune escape

Research Project

Project/Area Number 16H05477
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University (2017-2018)
Kindai University (2016)

Principal Investigator

Mandai Masaki  京都大学, 医学研究科, 教授 (80283597)

Co-Investigator(Kenkyū-buntansha) 西尾 和人  近畿大学, 医学部, 教授 (10208134)
村上 隆介  京都大学, 医学研究科, 特定病院助教 (40782363)
宮澤 正顯  近畿大学, 医学部, 教授 (60167757)
馬場 長  京都大学, 医学研究科, 准教授 (60508240)
濱西 潤三  京都大学, 医学研究科, 講師 (80378736)
中井 英勝  近畿大学, 医学部, 講師 (20441082)
鈴木 彩子  近畿大学, 医学部, 講師 (90378696)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2016: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords卵巣癌 / 腫瘍免疫 / ゲノム診断 / 抗腫瘍免疫 / 腫瘍ゲノム / ゲノム多様性 / 免疫 / 免疫療法 / 腫瘍内ゲノム多様性 / 包括的遺伝子発現解析
Outline of Final Research Achievements

The aim of this study was to establish the tumor genome analysis pipeline using clinical tumor tissue for actual clinical setting. Moreover, we aimed to identify tumor genome biomarkers for stimulating immune activity to conquer cancer. The fruit of this research is to establish the platform of genome and transcriptome analyses by means of tumor tissue including tumor microenvironment and ,moreover to investigete biomarkers of immune reaction associated with somatic genome alteration. For the clinical utility, we established the multi platform pipeline in the tumor omics analyses.
The diversity scores in cancer genome alteration including mutation and copy number alteration predicted prognoses. Stratification of genome alterations was integrated with transcriptome analyses reflecting the activity of tumor immunity. Diversity scores related with response to treatment was utilized from blood samples over the course of treatment by T cells and B cells repertoires analyses.

Academic Significance and Societal Importance of the Research Achievements

がんゲノム診断が実用化されつつある。本研究では実臨床において腫瘍組織から得られたDNAを用いたゲノムデータから遺伝子変異の多用性を算出する方法を用いてがんゲノムの多様性と腫瘍免疫の応答性との関連を検討した。腫瘍組織から得られたRNAを用いた免疫プロファイルを用いて癌遺伝子の多様性スコアとの相関が観測できた。これらは卵巣癌に対する予後や薬物治療の効果と関連することが示唆される。高額な薬剤が一定の効果を示しているが、本研究の手法を用いて個別化することで治療の感受性予測マーカーや反応性を表すマーカーにつながる可能性があり、非常に有用な研究であったと考える。今後さらなる検証と研究の発展が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Early feasibility surveillance of gynecologic robotic‐assisted surgeries in Japan2019

    • Author(s)
      Baba Tsukasa、Mandai Masaki、Nishi Hirotaka、Nishii Osamu、Kitawaki Jo、Sawada Morio、Isaka Keiichi、Fujii Tomoyuki
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 45 Issue: 4 Pages: 787-793

    • DOI

      10.1111/jog.13923

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VISTA expressed in tumour cells regulates T cell function2018

    • Author(s)
      Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
    • Journal Title

      British Journal of Cancer

      Volume: 120 Issue: 1 Pages: 115-127

    • DOI

      10.1038/s41416-018-0313-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum‐Resistant Ovarian Cancer2018

    • Author(s)
      Inayama Yoshihide、Hamanishi Junzo、Matsumura Noriomi、Murakami Ryusuke、Abiko Kaoru、Yamaguchi Ken、Baba Tsukasa、Horie Katsuyuki、Konishi Ikuo、Mandai Masaki
    • Journal Title

      The Oncologist

      Volume: 23 Issue: 11 Pages: 1382-1384

    • DOI

      10.1634/theoncologist.2018-0167

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression.2018

    • Author(s)
      Lin H, Wei S, Hurt EM, Green MD, Zhao L, Vatan L, Szeliga W, Herbst R, Harms PW, Fecher LA, Vats P, Chinnaiyan AM, Lao CD, Lawrence TS, Wicha M, Hamanishi J, Mandai M, Kryczek I, Zou W.
    • Journal Title

      J Clin Invest

      Volume: Apr 2;128(4) Issue: 4 Pages: 1708-1708

    • DOI

      10.1172/jci120803

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cancer immunotherapies targeting the PD-1 signaling pathway2017

    • Author(s)
      Iwai Yoshiko、Hamanishi Junzo、Chamoto Kenji、Honjo Tasuku
    • Journal Title

      J Biomed Sci.

      Volume: 24 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s12929-017-0329-9

    • NAID

      120006309287

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonal composition of human ovarian cancer based on copy number analysis reveals a reciprocal relation with oncogenic mutation status.2017

    • Author(s)
      Sakai K, Ukita M, Schmidt J, Wu L, De Velasco MA, Roter A, Jevons L, Nishio K, Mandai M.
    • Journal Title

      Cancer Lett

      Volume: 1;405 Pages: 22-28

    • DOI

      10.1016/j.canlet.2017.07.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] PD-1 signal blockade for ovarian cancer: Perspectives and issues2017

    • Author(s)
      Hamanishi J
    • Organizer
      The 1st J-K-T Joint Conference of Obstetrics and Gynecology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Specific gene signatures and oligoclonal expansion of B cell repertoire with the responders of anti-PD-1 antibody (Nivolumab) for ovarian cancer; Novel predictive biomarkers.2017

    • Author(s)
      Hamanishi J, Murakami R, Mandai M, Matsumura M, Abiko K, Baba T, Hosoe Y, Yamaguchi K, Konishi I.
    • Organizer
      International Symposium on Immune Diversity and Cancer Therapy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multi-omics analysis of anti-PD-1 antibody (Nivolumb) treated patients with ovarian cancer (PD-1経路阻害薬に対するマルチオミクス解析とバイオマーカー探索).2017

    • Author(s)
      Hamanishi J
    • Organizer
      日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 白金薬耐性の再発卵巣癌に対して次に実施する化学療法での抗PD-1抗体であるニボルマブを用いた治療の効果(The impact of anti-PD-1 antibody Nivolumab on subsequent chemotherapy in platinum-resistant recurrent ovarian cancer)2017

    • Author(s)
      稲山嘉英、濱西潤三、松村謙臣、安彦郁、村上隆介、山口建、馬場長、小西郁生、万代昌紀
    • Organizer
      日本癌治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 上皮性卵巣癌におけるコピー数多型と腫瘍クローン数についての検討2016

    • Author(s)
      高矢寿光、坂井和子、浮田真沙世、中井英勝、西尾和人、万代昌紀
    • Organizer
      日本産科婦人科遺伝診療学会
    • Place of Presentation
      メルパルク京都(京都市)
    • Year and Date
      2016-12-16
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi