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Formation and maintenance of tertiary lymphoid organs

Research Project

Project/Area Number 18K07008
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-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, 中央病院, 科長 (40276217)

Co-Investigator(Kenkyū-buntansha) 中嶋 幸生  国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (80785775)
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) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膵がん / 腫瘍免疫 / 免疫微小環境 / 神経 / 3次リンパ装置 / 微小環境 / 神経束 / 免疫
Outline of Final Research Achievements

The cancer microenvironment contributes to the biological characteristics of cancer. In this study, we compared two types of tertiary lymphoid organs (TLOs) formed in pancreatic cancer tissues, and suggested that the formation and maintenance of both types of TLOs are highly related to the nervous system. Examination of nerve alterations in pancreatic cancer tissues showed that nerve fiber density was significantly decreased in pancreatic cancer tissues, and decreased nerve fiber density was an independent poor prognostic factor. It was suggested that the cause of the decrease in nerve fibers was related to the invasive capacity of the cancer and also to the mechanism of formation and maintenance of the TLOs. In addition, common and uncommon features were found in the formation of the TLOs in pancreatic cancer tissues and non-neoplastic chronic inflammatory tissues, suggesting the possibility of a regulatory mechanism specific to each tissue.

Academic Significance and Societal Importance of the Research Achievements

がん微小環境はがんの生物学的特性の決定に寄与し、その形成機序の解明はがんの生物学の解明とがん治療の標的探索に重要である。本研究では難治性膵がんを対象に、がん微小環境における3次リンパ装置に注目し、その形成・維持と神経との関係、またがん微小環境の神経変化について検討し、これまで知られていなかった事象を新しく見出した。3次リンパ装置形成は免疫治療奏功性の予測や奏功性指標となる。本研究により発見された事象をさらに深く検討することにより、膵がんの診断・治療効果の向上につながることが期待される。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)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results)

  • [Journal Article] Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer.2020

    • Author(s)
      Hiraoka N, Nitta H, Ohba A, Yoshida H, Morizane C, Okusaka T, Nara S, Esaki M, Kishi Y, Shimada K.
    • Journal Title

      Hum Pathol

      Volume: 105 Issue: 1 Pages: 9-19

    • DOI

      10.1080/2162402x.2020.1838812

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological significance of core 3 O-glycan synthetic enzyme, β1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma.2020

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

      PLoS One

      Volume: 15 Issue: 11 Pages: e0242851-e0242851

    • DOI

      10.1371/journal.pone.0242851

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of classical HLA class I antigens, HLA-E, and HLA-G is adversely prognostic in pancreatic cancer patients.2020

    • Author(s)
      Hiraoka N, Ino Y, Hori S, Yamazaki-Itoh R, Naito C, Shimasaki M, Esaki M, Nara S, Kishi Y, Shimada K, Nakamura N, Torigoe T, Heike Y.
    • Journal Title

      Cancer Sci.

      Volume: in press Issue: 8 Pages: 3057-3070

    • DOI

      10.1111/cas.14514

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma.2019

    • Author(s)
      Iwasaki T, Hiraoka N, Ino Y, Nakajima K, Kishi Y, Nara S, Esaki M, Shimada K, Katai H.
    • Journal Title

      Cancer Sci.

      Volume: 110 Issue: 4 Pages: 1491-1502

    • DOI

      10.1111/cas.13975

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies.2019

    • Author(s)
      Ino Y, Oguro S, Yamazaki-Itoh R, Hori S, Shimada K, Hiraoka N
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 10 Pages: 1149-1159

    • DOI

      10.18632/oncotarget.26646

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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