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Biological roles of neural system in pancreatic tumor immune microenvironment

Research Project

Project/Area Number 21K07139
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Hiraoka Nobuyoshi  国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (40276217)

Co-Investigator(Kenkyū-buntansha) 石川 義典 (猪野義典)  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (90291137)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん微小環境 / 免疫系 / 神経系 / 膵がん / 末梢神経 / 免疫微小環境 / 神経 / 腫瘍免疫
Outline of Research at the Start

がん間質の免疫微小環境はがんの生物学と密接な関係にある。免疫微小環境はがん細胞と免疫系のみならず、神経系、血管系等の多様な要因が制御に関わり、各系統間の関係性の把握がその理解につながる。最近、われわれは膵がん組織内では神経密度低下が生じ、それが予後不良因子になることを示した。本研究では神経系の役割を中心に膵がん免疫微小環境形成・制御の理解を深めるため、神経密度低下を呈する膵がんとそうでない膵がん組織を比較検討する。本研究により、がん微小環境形成の一端に迫れると共に、がん免疫活性化手段の一助となってがん免疫療法に役立つことが期待される。

Outline of Final Research Achievements

The immune microenvironment of the cancer stroma is closely related to cancer biology. This study aims to understand pancreatic cancer microenvironment formation and regulation, focusing on the role of the nervous system. Sympathetic, parasympathetic, and sensory nerve density in pancreatic cancer tissue was significantly associated with patient prognosis by the nervous system. The results of a comprehensive gene expression analysis of pancreatic cancer tissues revealed a close association between the nervous system and the immune system. The specific nervous system was considered to be deeply involved in the formation of the pancreatic cancer immune microenvironment.

Academic Significance and Societal Importance of the Research Achievements

本研究により、ヒト膵がん間質の免疫微小環境を特徴付ける分子とそれら免疫微小環境を誘導する分子機序が明らかとなれば、がん生物学の理解を深める学術的意義にとどまらず、既存の免疫療法の問題点を克服し、効果的な免疫療法の開発や分子標的治療の開発、がんの予後予想の開発に寄与するものと期待される。また膵がんは、今もって罹患率と死亡率がほぼ同値を示す極めて難治性のがんであり、早期診断方法や効果的な治療法の確立が早急に望まれていることから、本研究により難治性膵がんの治療選択肢が広がるようになれば、国民の保険・医療に寄与するところが大きい。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2024 2023 2022 2021

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results)

  • [Journal Article] Correlation of Vein-Rich Tumor Microenvironment of Intrahepatic Cholangiocarcinoma With Tertiary Lymphoid Structures and Patient Outcome2024

    • Author(s)
      Doi N, Ino Y, Fuse M, Esaki M, Shimada K, Hiraoka N
    • Journal Title

      Mod Pathol

      Volume: 37 Issue: 2 Pages: 100401-100401

    • DOI

      10.1016/j.modpat.2023.100401

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel insights into the intraepithelial spread of extrahepatic cholangiocarcinoma: clinicopathological study of 382 cases on extrahepatic cholangiocarcinoma2023

    • Author(s)
      Nagashima D, Esaki M, Nara S, Ban D, Takamoto T, Mizui T, Shimada K, Hiraoka N
    • Journal Title

      Front Oncol

      Volume: 13 Pages: 1216097-1216097

    • DOI

      10.3389/fonc.2023.1216097

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas: Carboxypeptidase A2, Carboxypeptidase A1, and Glycoprotein 2.2023

    • Author(s)
      Ishimoto-Namiki U, Ino Y, Esaki M, Shimada K, Saruta M, Hiraoka N.
    • Journal Title

      Am J Surg Pathol.

      Volume: 47 Issue: 5 Pages: 525-534

    • DOI

      10.1097/pas.0000000000002024

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5.2022

    • Author(s)
      Nakajima K, Ino Y, Naito C, Nara S, Shimasaki M, Ishimoto U, Iwasaki T, Doi N, Esaki M, Kishi Y, Shimada K, Hiraoka N.
    • Journal Title

      Br J Cancer

      Volume: 126 Issue: 4 Pages: 628-639

    • DOI

      10.1038/s41416-021-01639-9

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel insights into immunohistochemical analysis for diagnosing serous neoplasm of the pancreas: aquaporin 1, stereocilin, and transmembrane protein 255B.2021

    • Author(s)
      Watase C, Fuse M, Ino Y, Naito C, Hiraoka N.
    • Journal Title

      Histopathology

      Volume: 79 Issue: 5 Pages: 872-879

    • DOI

      10.1111/his.14456

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association between the expression of core 3 synthase and survival outcomes of patients with cholangiocarcinoma.2021

    • Author(s)
      Boottanun P, Ino Y, Shimada K, Hiraoka N, Angata K, Narimatsu H.
    • Journal Title

      Oncol Lett.

      Volume: 22 Issue: 5 Pages: 760-760

    • DOI

      10.3892/ol.2021.13021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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