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Investigation of the metastatic mechanisms in spread through air spaces (STAS) in lung cancer

Research Project

Project/Area Number 20K17742
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionShinshu University

Principal Investigator

Eguchi Takashi  信州大学, 学術研究院医学系(医学部附属病院), 講師 (50447744)

Project Period (FY) 2020-04-01 – 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: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肺癌 / 経気腔進展 / 腫瘍免疫 / 微小環境 / STAS / 転移 / TMA / 腫瘍微小環境
Outline of Research at the Start

近年、早期肺癌に対する肺切除術が増加しているが、術後に局所再発や遠隔転移を起こす症例も未だに多い。肺癌細胞が気道を経由して広がる経気腔進展(spread through air spaces, STAS)が最近注目され、肺癌切除後の局所再発・遠隔転移への関与が報告されている。しかし、STAS形成の機序に関しては未だ不明な点が多い。
本研究では、癌転移における"seed and soil"説に基づき、STAS部における癌細胞側(seed)の因子としての上皮間葉転換や、それを受け入れる微小環境(soil)としての免疫細胞浸潤を検討し、STAS形成における分子生物学的・免疫学的機序を解明する。

Outline of Final Research Achievements

[Research on STAS and Immune Cell Distribution] We created a tissue microarray (TMA) from 301 primary lung cancers. We evaluated tumor infiltration of immune cells using this TMA, focusing on their distribution within the tumor. We discovered that cases where anti-tumor immune cells (e.g., CD8-positive T cells) cannot migrate into the tumor have poor prognoses and that FoxP3-positive T cells at the tumor margin are prognostic factors in STAS-positive lung cancer. These results were presented at the World Conference on Lung Cancer in August 2022 and have been submitted for publication in Heliyon, currently under the second revision.

[STAS Evaluation Using Frozen Specimens] To diagnose STAS intraoperatively, we conducted a prospective study evaluating the sensitivity and specificity of 114 frozen specimens. The results were presented at the World Conference on Lung Cancer in August 2022 and published in JTCVS Techniques 2023.

Academic Significance and Societal Importance of the Research Achievements

本研究は、肺癌におけるSTASと免疫細胞分布の関係を明らかにし、STAS陽性症例の予後不良に関与する免疫細胞の動態を解明した。特に腫瘍内への抗腫瘍免疫脂肪の浸潤障害と、腫瘍辺縁部における腫瘍促進免疫細胞とSTASの共存が重要な予後規定因子であることを発見した。また、術中迅速診断によるSTAS検出の実現可能性を確認した。
本研究の成果は、STASの術中診断精度を向上させ、患者の予後を予測し、治療方法を選択するための新たなバイオマーカーの開発に寄与すると考える。これにより個別化治療の向上や術後管理の最適化、ひいては患者の生存率向上と医療資源の効率的活用につながる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2024 2022 2021

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Improving intraoperative diagnosis of spread through air spaces: A cryo-embedding-medium inflation method for frozen section analysis2024

    • Author(s)
      Takashi Eguchi, Shunichiro Matsuoka, Mai Iwaya, Shota Kobayashi, Maho Seshimoto, Shuji Mishima, Daisuke Hara, Hirotaka Kumeda, Kentaro Miura, Kazutoshi Hamanaka, Takeshi Uehara, Kimihiro Shimizu
    • Journal Title

      JTCVS Techniques

      Volume: - Pages: 170-176

    • DOI

      10.1016/j.xjtc.2024.02.014

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Immune-cell distribution between tumor edge and center affects lung cancer aggressiveness; Multiplex immunofluorescence2022

    • Author(s)
      Takashi Eguchi
    • Organizer
      2022 World Conference on Lung Cancer
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Accurate intraoperative diagnosis of spread through air spaces (STAS) using a cryo-embedding-medium inflation method2022

    • Author(s)
      Takashi Eguchi
    • Organizer
      2022 World Conference on Lung Cancer
    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immune-cell distribution between tumor edge and center affects lung cancer aggressiveness - Multiplex immunofluorescence2022

    • Author(s)
      Takashi Eguchi
    • Organizer
      2022 World Conference on Lung Cancer
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Seed and soil説に基づく肺癌・経気腔進展(STAS)の機序解明の試み2021

    • Author(s)
      江口隆、松岡峻一郎、竹田哲、三浦健太郎、濱中一敏、上原剛、清水公裕
    • Organizer
      日本癌病態治療研究会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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