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Elucidating the natural history of cfDNA and its impact on anti-tumor immunity

Research Project

Project/Area Number 20K16448
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Nakashima Chiho  佐賀大学, 医学部附属病院, 病院助教 (40858502)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
KeywordscfDNA / 非小細胞肺癌 / 免疫チェックポイント阻害薬 / cfDNA濃度 / 肺がん / cfNDA / DAMPs / Lung cancer / STING
Outline of Research at the Start

従来、がんにおける循環血漿DNA研究はその中に含まれるがん細胞由来の遺伝子変異を検出することにFocusされてきた。我々は先行研究により、免疫原性の低い細胞死であるアポトーシスとは起源を異にするLong fragment DNAを血漿中に発見・報告しており、進行担がん状態においてはこの免疫反応惹起物質たり得る循環血漿DNAが持続的かつ過剰に存在することが免疫反応・炎症病態に影響を与える可能性がある。本研究においては進行担がん患者で観察される循環血漿中DNA濃度の上昇そのものが抗腫瘍免疫に与える影響を明らかにし、免疫チェックポイント阻害薬の効果予測・有害事象予測因子となりうるか検討する。

Outline of Final Research Achievements

Since circulating plasma DNA (cfDNA) was detected at high concentrations in the peripheral blood of patients with carcinoma, it was assumed that these DNAs may act as DAMPs and contribute to systemic inflammation. Therefore, we retrospectively examined the association of cfDNA size and concentration with white blood cell count, CRP, neutrophil/lymphocyte ratio, immune checkpoint inhibitor efficacy, and presence of immune-related adverse events in 33 patients with advanced-stage lung cancer, but no significant correlation was found. We need to go back to local tumor analysis. We currently examine the relationship between the microenvironment and tumor gene abnormalities using the Boston Gene tumor portrait and the Cancer Pathway Index.

Academic Significance and Societal Importance of the Research Achievements

担癌状態で生じる高炎症状態は必ずしも循環血漿DNA濃度の増加とは相関していなかった。また、循環血漿DNA濃度の多寡で免疫チェックポイント阻害薬の効果を予測することは困難であった。腫瘍局所での炎症状態について検討する必要があると考えられ、現在、免疫微小環境解析を用いた検討を行っている。

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

    (4 results)

All 2024 2023 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Funded Workshop (2 results)

  • [Journal Article] Advanced non-small cell lung cancer patient with a complete response and allergic immune-related adverse events by combined immunotherapy, including anti-CTLA-4 and anti-PD-1 antibodies: A case report2024

    • Author(s)
      Chiho Nakashima et al.
    • Journal Title

      Current Problems in Cancer: Case Reports

      Volume: - Pages: 100298-100298

    • DOI

      10.1016/j.cpccr.2024.100298

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALDH2 polymorphism rs671 is a predictor of PD-1/PD-L1 inhibitor efficacy against thoracic malignancies2021

    • Author(s)
      Akiko Matsumoto, Chiho Nakashima, Shinya Kimura, Eizaburo Sueoka, Naoko Aragane
    • Journal Title

      BMC Cancer

      Volume: 21 Issue: 1 Pages: 584-595

    • DOI

      10.1186/s12885-021-08329-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Funded Workshop] American Association for Cancer Research 20232023

    • Related Report
      2023 Annual Research Report
  • [Funded Workshop] The 82nd Annual meeting of the Japanese cancer association2023

    • Related Report
      2023 Annual Research Report

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

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