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Research for novel biomarkers and therapeutic targets related to cancer microenvironment in pancreatic cancer

Research Project

Project/Area Number 20K17620
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionYamaguchi University

Principal Investigator

Matsui Hiroto  山口大学, 医学部附属病院, 助教 (60780781)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords癌免疫 / 癌微小環境 / 膵癌 / 免疫療法 / がん微小環境 / バイオマーカー / 抑制性免疫 / 癌代謝
Outline of Research at the Start

①免疫療法を施行した膵癌切除症例を予後良好群:6例(OS 3年以上)、不良群:5例(OS 1年未満)に分けRNAシークエンスを行い、Hallmarkgene sets を用いたGSEA法で解析した結果、解糖系に関連する発現遺伝子群が高発現していた。その中でも免疫抑制に関連すると報告されているIL13Rに着目した。②IL13Raによる免疫染色を膵癌切除標本にて行う。③膵癌切除標本を用いたqPCRによる定量と予後の解析を行う。④IL13Raをノックイン/ノックダウンした細胞株を用いてin vitroでの機能解析を行う。

Outline of Final Research Achievements

Initially, we planned to perform immunostaining on the immunotherapy-treated group, but as the samples of cases were mostly old and the paraffin blocks were not in good condition, the accurate assessment by immunostaining was questionable.
Therefore, we have previously focused on a molecule that appears to be involved in cancer stem cells: calreticulin, and examined its association with immune escape mechanisms in pancreatic cancer cells that express high levels of calreticulin. The results showed that PDL1 expression was higher and HLA-class1 expression was lower in the Calreticulin-expressing cell lines, suggesting that pancreatic cancer stem cells with high cell surface expression of Calreticulin may be involved in escape from immune surveillance.

Academic Significance and Societal Importance of the Research Achievements

膵癌におけるCalreticulin発現は膵癌幹細胞に対するマーカーであるとともに免疫逃避に関するバイオマーカーともなりうる。同時に今後、免疫チェックポイント阻害剤に対する治療効果予測の可能性ともなりうる。
また、今後、免疫逃避機構におけるカスケードとCalreticulinの関与を検証することにより膵癌に対する免疫チェックポイント阻害剤の治療効果の向上も期待できる。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2021 2020

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] Pancreatic Cancer Stem-Like Cells With High Calreticulin Expression Associated With Immune Surveillance2021

    • Author(s)
      Fujiwara Yasuhiro、Tsunedomi Ryouichi、Yoshimura Kiyoshi、Matsukuma Satoshi、Fujiwara Nobuyuki、Nishiyama Mitsuo、Kanekiyo Shinsuke、Matsui Hiroto、Shindo Yoshitaro、Tokumitsu Yukio、Yoshida Shin、Iida Michihisa、Suzuki Nobuaki、Takeda Shigeru、Ioka Tatsuya、Hazama Shoichi、Nagano Hiroaki
    • Journal Title

      Pancreas

      Volume: 50 Issue: 3 Pages: 405-413

    • DOI

      10.1097/mpa.0000000000001772

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial2020

    • Author(s)
      Hiroto Matsui、Hazama Shoichi、Nakajima Masao、Xu Ming、Matsukuma Satoshi、Tokumitsu Yukio、Shindo Yoshitaro、Tomochika Shinobu、Yoshida Shin、Iida Michihisa、Suzuki Nobuaki、Takeda Shigeru、Yoshino Shigefumi、Ueno Tomio、Oka Masaaki、Nagano Hiroaki
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 70 Issue: 4 Pages: 945-957

    • DOI

      10.1007/s00262-020-02737-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial.2020

    • Author(s)
      Masao;Nakajima, Shoichi, Hazama; Koji;Tamada. Nobuaki;Suzuki.Hiroaki;Nagano
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 5 Issue: 8 Pages: 5-10

    • DOI

      10.1007/s00262-020-02518-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 免疫チェックポイント阻害剤を基軸とした汎用性の高い新規免疫治療の開発2020

    • Author(s)
      松井洋人
    • Organizer
      第75回日本消化器外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 樹状細胞ワクチンによる肝細胞癌術後補助療法(第I/II相臨床試験)-最終報告と今後の展望-2020

    • Author(s)
      松井洋人
    • Organizer
      第41回癌免疫外科研究会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2023-01-30  

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