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Phenotyping of white blood cells contributing to tumor immunity activated by pemetrexed

Research Project

Project/Area Number 20K16453
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Takagi Haruhi  順天堂大学, 大学院医学研究科, 非常勤助教 (40868907)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsペメトレキセド / 免疫チェックポイント分子 / テロメラーゼ活性 / 腫瘍免疫応答誘導 / 非扁平非小細胞肺がん / 非扁平小細胞肺がん / 免疫チェックポ イント分子
Outline of Research at the Start

白血球のプロファイリングは免疫系の変化を鋭敏に反映するため、テロメラーゼ活性の亢進白血球、PD-1白血球の定量は、鋭敏なICI奏効予測マーカーとなり、将来的な、PEM及びPEM+ICI併用療法の個別化治療選択に応用が可能となる。少量採血による診断システムは即座に他科のがん診断にも応用可能であり、将来的には非侵襲的がん診断法として肺がん研究にとどまらず、さまざまながん種へ展開することを目指す。本システムの実現によって治療奏効率の向上と生存期間の延長で国民生活の質の向上と高額ながん医療コストの節減による社会経済の発展に貢献できることが見込まれ、本研究の学術的意義は非常に大きい。

Outline of Final Research Achievements

We evaluated the clinical characteristics and predictive factors in patients with advanced non-squamous non-small-cell lung cancer who underwent long-term Pemetrexed (PEM) maintenance therapy. The long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group. Increased PD-1 lymphocytes were associated with the long-term PEM response group. These results suggest PEM is related to PD-1 lymphocyte mediated tumor immunity. Moreover, we focused on the monocytic cells with high telomerase activity in the lung cancer patients.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、白血球のプロファイリングは免疫系の変化を鋭敏に反映するため、テロメラーゼ活性の亢進白血球、PD-1白血球の定量は、鋭敏なICI奏効予測マーカーとなり、将来的な、PEM及びPEM+ICI併用療法の個別化治療選択に応用が可能となる。少量採血による診断システムは即座に他科のがん診断にも応用可能であり、将来的には非侵襲的がん診断法として肺がん研究にとどまらず、さまざまながん種へ展開することを目指す。本システムの実現によって治療奏効率の向上と生存期間の延長で国民生活の質の向上と高額ながん医療コストの節減による社会経済の発展に貢献できることが見込まれ、本研究の学術的意義は非常に大きい。

Report

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

    (3 results)

All 2022 2021

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

  • [Journal Article] The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force2022

    • Author(s)
      Wang Qingbo S.、et al.
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 4830-4830

    • DOI

      10.1038/s41467-022-32276-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DOCK2 is involved in the host genetics and biology of severe COVID-192022

    • Author(s)
      Namkoong Ho、et al.
    • Journal Title

      Nature

      Volume: 609 Issue: 7928 Pages: 754-760

    • DOI

      10.1038/s41586-022-05163-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High lymphocyte population-related predictive factors for a long-term response in non-small cell lung cancer patients treated with pemetrexed: a retrospective observational study2021

    • Author(s)
      Sumiyoshi Issei、Okabe Takahiro、Togo Shinsaku、Takagi Haruhi、Motomura Hiroaki、Ochi Yusuke、Shimada Naoko、Haraguchi Mizuki、Shibayama Rina、Fujimoto Yuichi、Watanabe Junko、Iwai Moe、Kadoya Kotaro、Iwakami Shin-ichiro、Takahashi Kazuhisa
    • Journal Title

      Journal of Translational Medicine

      Volume: 19 Issue: 1 Pages: 92-92

    • DOI

      10.1186/s12967-021-02761-1

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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