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Combination immunotherapy targeting for chemoresistnat cancer stem cells with PD-L1 expression

Research Project

Project/Area Number 16K19927
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

URAKAWA SHINYA  大阪大学, 医学部附属病院, 医員 (40768975)

Project Period (FY) 2016-04-01 – 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords食道癌 / 癌幹細胞 / PD-L1 / 抗腫瘍免疫回避機構 / PD-1 / PDL1 / 幹細胞 / 抗腫瘍免疫 / 治療抵抗性
Outline of Final Research Achievements

Although immunohistochemistry showed tumorous PD-L1 expression was associated with poor overall survival in esophageal cancer patients who underwent esophagectomy, no relationship was identified between PD-L1 expression and presence of preoperative therapy or tumor response. In flow cytometry analysis of tissue-infiltrating lymphocytes extracted from pre-therapeutic biopsy tissue and resected specimen, percentage of positive PD-1 in CD8+ cells was higher in non-responders compared with responders while some cases showed increased PD-1-expression after chemotherapy, thus indicating that PD-L1/PD-1 pathways was associated with chemoresistance in esophageal cancer. Now, we are analyzing PD-L1 expression in pre-therapeutic biopsy tissue by immunohistochemistry and establishing a new method to culture tumor tissue together with immune cells to investigate the mechanism of cancer stem cells with PD-L1-expression resistant to chemotherapy.

Report

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

    (4 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer2017

    • Author(s)
      Momose Kota、Yamasaki Makoto、Tanaka Koji、Miyazaki Yasuhiro、Makino Tomoki、Takahashi Tsuyoshi、Kurokawa Yukinori、Nakajima Kiyokazu、Takiguchi Shuji、Mori Masaki、Doki Yuichiro
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 1 Pages: 958-964

    • DOI

      10.3892/ol.2017.6215

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 食道がん腫瘍組織内免疫関連因子を用いた術前化学療法効果予測2018

    • Author(s)
      浦川真哉
    • Organizer
      食道学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 食道がんのバイオマーカー DCF療法の効果予測としての免疫担当細胞の解析2016

    • Author(s)
      武岡 奉均
    • Organizer
      日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-20
    • Related Report
      2016 Research-status Report
  • [Presentation] 食道がんのバイオマーカー 食道癌におけるMLH-1発現と化学療法の有効性についての検討2016

    • Author(s)
      百瀬 洸太
    • Organizer
      日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-20
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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