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Development of new immunotherapy to increase tumor infiltrating T cells in conventional pancreatic cancer

Research Project

Project/Area Number 19K16840
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionYokohama City University

Principal Investigator

KATO Shingo  横浜市立大学, 附属病院, 講師 (20622583)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膵癌 / 腫瘍免疫 / 腫瘍浸潤リンパ球 / オルガノイド
Outline of Research at the Start

免疫チェックポイント阻害剤(Immune Checkpoint Inhibitor; ICI)は、様々ながん種に適応が拡大されているが、難治がんである膵癌では、複数の臨床試験で腫瘍縮小効果が認められていない。ICIが高い抗腫瘍能を発揮するためには、多くの腫瘍特異的細胞障害性T細胞が腫瘍局所に存在する必要があるが、ほとんどの膵癌では腫瘍浸潤リンパ球(Tumor infiltrating lymphocyte; TIL)が極めて少ない。本研究では、独自に樹立した遺伝子変異の少ないマウス膵癌オルガノイド細胞株を用いて、遺伝子変異が少ない通常の膵癌に対してTILを増加させる手法の開発を目指す。

Outline of Final Research Achievements

In this study, we aimed to develop an effective cancer immunotherapy for conventional pancreatic cancer with few genetic mutations. Within the research period, we identified a chemokine whose secretion is significantly increased in pancreatic cancer cell organoids from secretome analysis of mouse pancreatic cancer organoids. Furthermore, using a mouse model of pancreatic cancer, we identified a tumor immunity-related gene from the signal transduction system of this chemokine that could be a therapeutic target. The growth of pancreatic cancer was significantly suppressed in knockout mice of this gene compared to wild-type mice as a host. In the future, we plan to examine the possibility of applying this gene as a therapeutic agent for pancreatic cancer by administering a substance that inhibits the function of this gene from outside the body.

Academic Significance and Societal Importance of the Research Achievements

難治癌である膵癌の新たな治療法開発の糸口となる所見を得た。腫瘍免疫療法は、原発臓器に関係なく効果が期待できる治療法である。しかし、膵癌においては治療効果が高くないという臨床試験の結果があり、現状では使用されていない。今回の研究で、膵癌に効果的な免疫療法の経路の一つを明らかにした。今後は、この経路を標的とした薬剤の開発を行い、臨床応用を目指すこととした。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Precision modeling of gall bladder cancer patients in mice based on orthotopic implantation of organoid-derived tumor buds2021

    • Author(s)
      Kato Shingo、Fushimi Kentaro、Yabuki Yuichiro、Maru Yoshiaki、Hasegawa Sho、Matsuura Tetsuya、Kurotaki Daisuke、Suzuki Akihiro、Kobayashi Noritoshi、Yoneda Masato、Higurashi Takuma、Enaka Makiko、Tamura Tomohiko、Hippo Yoshitaka、Nakajima Atsushi
    • Journal Title

      Oncogenesis

      Volume: 10 Issue: 4 Pages: 30-30

    • DOI

      10.1038/s41389-021-00322-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent Advances in Implantation-Based Genetic Modeling of Biliary Carcinogenesis in Mice2021

    • Author(s)
      Izumiya Masashi、Kato Shingo、Hippo Yoshitaka
    • Journal Title

      Cancers

      Volume: 13 Issue: 10 Pages: 2292-2292

    • DOI

      10.3390/cancers13102292

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of Biomarkers and Imaging for Early Detection of Pancreatic Cancer2020

    • Author(s)
      Kato Shingo、Honda Kazufumi
    • Journal Title

      Cancers

      Volume: 12 Issue: 7 Pages: 1965-1965

    • DOI

      10.3390/cancers12071965

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CA19-9 as a therapeutic target in pancreatitis.2019

    • Author(s)
      Shingo Kato, Kazufumi Honda
    • Journal Title

      Annals of translational medicine

      Volume: 7 Issue: S8 Pages: S318-S318

    • DOI

      10.21037/atm.2019.09.161

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional analysis of pancreatic fat by fat-water magnetic resonance imaging provides detailed characterization of pancreatic steatosis with improved reproducibility2019

    • Author(s)
      Kato Shingo、Iwasaki Akito、Kurita Yusuke、Arimoto Jun、Yamamoto Toh、Hasegawa Sho、Sato Takamitsu、Imajo Kento、Hosono Kunihiro、Kobayashi Noritoshi、Yoneda Masato、Higurashi Takuma、Kubota Kensuke、Utsunomiya Daisuke、Nakajima Atsushi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 12 Pages: e0224921-e0224921

    • DOI

      10.1371/journal.pone.0224921

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Organoid-based ex vivo reconstitution of Kras-driven pancreatic ductal carcinogenesis2019

    • Author(s)
      Matsuura Tetsuya、Maru Yoshiaki、Izumiya Masashi、Hoshi Daisuke、Kato Shingo、Ochiai Masako、Hori Mika、Yamamoto Shogo、Tatsuno Kenji、Imai Toshio、Aburatani Hiroyuki、Nakajima Atsushi、Hippo Yoshitaka
    • Journal Title

      Carcinogenesis

      Volume: - Issue: 4 Pages: 1-12

    • DOI

      10.1093/carcin/bgz122

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 抗腫瘍製剤の開発と効能評価を目的としたマウス胆嚢癌オルガノイドの同所移植モデルの確立2020

    • Author(s)
      加藤真吾、松浦哲也、黒滝大翼、筆宝義隆、田村智彦、中島淳
    • Organizer
      日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗腫瘍製剤スクリーニングのための膵癌患者モデルの開発2020

    • Author(s)
      加藤真吾、鈴木章浩、松浦哲也、筆宝義隆、中島淳
    • Organizer
      日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] DEVELOPMENT OF A NOVEL GALLBLADDER CANCER MOUSE MODEL USING ORGANOID CELL LINES2019

    • Author(s)
      Shingo Kato, Tetsuya Matura, Atsushi Nakajima
    • Organizer
      Digestive Disease Week
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] Precision mouse model

    • URL

      https://cancercommunity.nature.com/users/shingo-kato

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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