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Low-dose gemcitabine induces major histocompatibility complex class I-related chain A/B expression and enhances an antitumor innate immune response in pancreatic cancer.

Research Project

Project/Area Number 25462106
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKanazawa University

Principal Investigator

Ohta Tetsuo  金沢大学, 医学系, 教授 (40194170)

Co-Investigator(Kenkyū-buntansha) Miyashita Tomoharu  金沢大学, 医学系, 助教 (30397210)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords膵癌 / 術前化学療法 / 免疫逃避機構 / MICA/B / Gemcitabine / Valpronic acid / 自然免疫機構 / MICA / 自然免疫
Outline of Final Research Achievements

We investigated the effect of gemcitabine (GEM), a key drug for pancreatic cancer treatment, on the expression of cell surface MICA/B in pancreatic cancer cells and resulting cytotoxicity of γδ T cells. MICA and CD16 expressions from resected pancreatic cancer patient specimens, which received neoadjuvant chemotherapy (NAC) with GEM, were analyzed by immunohistochemistry. Immunohistochemical staining demonstrated that MICA expression in tumor cells and CD16 positive cells surrounding tumors were significantly higher in the NAC group compared to that of the control group. The present results indicate that low-dose GEM-induced MICA/B expression enhances innate immune function rather than cytotoxicity in pancreatic cancer. In addition, our result suggests that the inhibition of cleavage and release of MIC molecules from the tumor surface could potentially improve NKG2D-dependent cytotoxicity.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2015 2013

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Low-dose gemcitabine induces major histicompatibility complex class Ⅰ-related chain A/B expression and enhances an antitumorinnate immune response in pancreatic cancer.2015

    • Author(s)
      Miyashita T, et al.
    • Journal Title

      Clin Exp Med

      Volume: EPub Issue: 1 Pages: 1-13

    • DOI

      10.1007/s10238-015-0394-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 膵癌における免疫化学療法の可能性2013

    • Author(s)
      宮下知治、田島秀浩、正司政寿、中沼伸一、酒井清祥、林 泰寛、中川原寿俊、高村博之、北川裕久、太田哲生
    • Journal Title

      癌と化学療法

      Volume: 40 Pages: 1600-1602

    • Related Report
      2013 Research-status Report
  • [Presentation] Low dose gemcitabine induces Major Histocompatibility complex class l-related chain A/B expression and activates γδT cell function in pancreatic cancer2015

    • Author(s)
      Miyashita T, Miki K, Maekawa R, Makino I, Oyama K, Tajima H, Takamura H, Fushida S, Ahmed AK, Duncan MD, Harmon JW, Ohta T.
    • Organizer
      The 61st Annual Congress of International College of Surgeons Japan Section
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gemcitabine induces Major Histocompatibility Complex Class I-related chain A/B expression, activating γδ T cell function in pancreatic cancer2015

    • Author(s)
      Miyashita T,  Miki K, Harmon JW, Ali K. Ahmed ,Tajima H, Fushida S, Ohta T
    • Organizer
      Digestive Disease Week 2015
    • Place of Presentation
      Washington(USA)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵癌化学療法による自然免疫誘導の可能性2013

    • Author(s)
      宮下知治,岡本浩一,酒井清祥,牧野 勇,中村慶史,林泰寛,尾山勝信,中川原寿俊,田島秀浩,高村博之,二宮 致,北川裕久,伏田幸夫,藤村 隆,太田哲生
    • Organizer
      第38回日本外科系連合学会学術集会
    • Place of Presentation
      東京、ハイアット リージェンシー 東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 膵癌における免疫細胞療法の新機軸を求めて-その基礎と臨床-2013

    • Author(s)
      宮下知治,中沼伸一、酒井清祥,牧野 勇,林 泰寛,中川原寿俊,田島秀浩,高村博之,北川裕久,藤村 隆,三木健次,竹村公延,前川隆司,梅田尚季,太田哲生
    • Organizer
      第44回日本膵臓学会大会
    • Place of Presentation
      仙台、仙台国際センター
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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