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Identification of T cell receptor repertoire profiling that define lung cancer risk

Research Project

Project/Area Number 21K19492
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionNational Cancer Center Japan

Principal Investigator

Shiraishi Kouya  国立研究開発法人国立がん研究センター, 研究所, 部門長 (80609719)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords肺がん / 生殖細胞系列変異 / TCRレパトア解析 / TCRレパトア / RNAシークエンス / 全エクソンシークエンス
Outline of Research at the Start

がん細胞は、HLA領域の欠失、遺伝子変異等の蓄積や免疫応答に関わる遺伝子群の発現異常といった複合的な遺伝子異常の蓄積により、がん細胞は宿主免疫から回避している。本研究では、肺腺がん症例約1600例を対象に既取得全エクソン・RNAシークエンスデータを用いたTCRレパトア解析を実施し、発がんリスク・予後・化学療法応答性それぞれに起因するプロファイルを明らかにする。また得られたデータを検証するため、別手法を用いてレパトアプロファイルを確認・同定する。

Outline of Final Research Achievements

We identified 19 LADC susceptibility loci, including several variants in the major histocompatibility complex region. The class I HLA-A*24:02 allele was identified as a risk factor for LADC and as conferring attenuated immunity. HLA-A*24:02 binds fewer somatic mutation-derived neoantigens in tumour cells than other HLA-A proteins, and loss of this allele occurs infrequently.
Next, we examined the correlation between T-cell receptor diversity (TCR repertoire profile) and lung cancer risk, especially for HLA risk alleles. Using approximately 2,500 RNA sequencing data obtained from previously acquired lung adenocarcinoma tissue specimens, we conducted the study using the MIXCR. We examined whether the RNA sequencing methods had any effect on the TCR repertoire profile, and we were able to detect the TCR repertoire profile, and we performed an integrated analysis focusing on the diversity of HLA alleles and TCR repertoire profile. The results are now being compiled.

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、様々な遺伝要因や環境要因等により免疫の活性化能に影響を与え、発がんリスクに寄与している可能性が示された。現在TCRレパトアの多様性は、免疫チェックポイント阻害剤など、一部の薬剤の治療効果や副作用等に影響を与えていることが報告されていることから、今後も重要な研究テーマであると考えられる。

Report

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

    (13 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 5 results) Presentation (1 results)

  • [Int'l Joint Research] アメリカがん研究所(NCI)/国際がん研究機関(IARC)/トロント大学(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy2023

    • Author(s)
      Shirasawa Masayuki、Yoshida Tatsuya、Shiraishi Kouya、et al.
    • Journal Title

      Lung Cancer

      Volume: 179 Pages: 107183-107183

    • DOI

      10.1016/j.lungcan.2023.107183

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma2023

    • Author(s)
      Higashiyama Masahiro、Motoi Noriko、Yotsukura Masaya、Yoshida Yukihiro、Nakagawa Kazuo、Yagishita Shigehiro、Shirasawa Masayuki、Yoshida Tatsuya、Shiraishi Kouya、Kohno Takashi、Ohe Yuichiro、Watanabe Shun‐ichi
    • Journal Title

      Pathology International

      Volume: 73 Issue: 5 Pages: 188-197

    • DOI

      10.1111/pin.13316

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASO Visual Abstract: Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma2022

    • Author(s)
      Yotsukura Masaya、Muraoka Yuji、Yoshida Yukihiro、Nakagawa Kazuo、Shiraishi Kouya、Kohno Takashi、Yatabe Yasushi、Watanabe Shun-ichi
    • Journal Title

      Annals of Surgical Oncology

      Volume: -

    • DOI

      10.1245/s10434-022-12718-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of tissue-of-origin of early stage cancers using serum miRNomes2022

    • Author(s)
      Matsuzaki Juntaro、Kato Ken、Oono Kenta、Tsuchiya Naoto、Sudo Kazuki、...、Kato Tomoyasu、et al.
    • Journal Title

      JNCI Cancer Spectrum

      Volume: 7 Issue: 1

    • DOI

      10.1093/jncics/pkac080

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma2022

    • Author(s)
      Yotsukura Masaya、Muraoka Yuji、Yoshida Yukihiro、Nakagawa Kazuo、Shiraishi Kouya、Kohno Takashi、Yatabe Yasushi、Watanabe Shun-ichi
    • Journal Title

      Annals of Surgical Oncology

      Volume: 30 Issue: 2 Pages: 851-858

    • DOI

      10.1245/s10434-022-12621-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants.2022

    • Author(s)
      Momozawa Yukihide、Sasai Rumi、Usui Yoshiaki、Taniyama Yukari、Parsons Michael T、Mizukami Keijiro、Sekine Yuya、Hirata Makoto、Kubo Michiaki、et al.
    • Journal Title

      JAMA Oncology

      Volume: 未定 Issue: 6 Pages: 871-871

    • DOI

      10.1001/jamaoncol.2022.0476

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Accounting for EGFR mutations in epidemiological analyses of non-small cell lung cancers: Examples based on the International Lung Cancer Consortium data2022

    • Author(s)
      Schmid S, Jiang M, Brown MC, Fares A, Garcia M, Soriano J, Dong M, Thomas S, Kohno T, etal.
    • Journal Title

      Cancer Epidemiol Biomarkers Prev

      Volume: 31 Issue: 3 Pages: 679-687

    • DOI

      10.1158/1055-9965.epi-21-0747

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping2021

    • Author(s)
      Teishikata Takashi、Shiraishi Kouya、Shinno Yuki、Kobayashi Yoshihisa、Kashima Jumpei、Ishiyama Takako、Yoshida Tatsuya、Mori Taisuke、Yatabe Yasushi
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 16 Issue: 12 Pages: 2133-2138

    • DOI

      10.1016/j.jtho.2021.07.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Immune-Related Microenvironment Determines Programmed Cell Death Protein-1/Programmed Death-Ligand 1 Blockade Efficacy in Patients With Advanced NSCLC2021

    • Author(s)
      Shirasawa Masayuki、Yoshida Tatsuya、Shimoda Yukiko、Takayanagi Daisuke、Shiraishi Kouya、Kubo Takashi、Mitani Sachiyo、Matsumoto Yuji、Masuda Ken、Shinno Yuki、Okuma Yusuke、Goto Yasushi、Horinouchi Hidehito、et al. and Motoi Noriko
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 16 Issue: 12 Pages: 2078-2090

    • DOI

      10.1016/j.jtho.2021.07.027

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term prognosis of patients with resected adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung.2021

    • Author(s)
      Yotsukura M, Asamura H, Motoi N, Kashima J, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI.
    • Journal Title

      J Thorac Oncol

      Volume: 16 Issue: 8 Pages: 1312-1320

    • DOI

      10.1016/j.jtho.2021.04.007

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A reply to “Lung cancer outcomes: Are BMI and race clinically relevant?”2021

    • Author(s)
      Liu Geoffrey、Brenner Hermann、Chen Chu、Christiani David、Field John K.、Hung Rayjean、Jie Zhang、Le Marchand Loic、Ryan Brid、Schabath Matthew B.、Schwartz Ann G.、Shete Sanjay、Shiraishi Kouya、Tardon Adonina、Teare M. Dawn、Yang Ping、Zhang Zuo-Feng、Xu Wei
    • Journal Title

      Lung Cancer

      Volume: 154 Pages: 225-226

    • DOI

      10.1016/j.lungcan.2021.02.019

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Identification of deleterious variants for adolescent and young adult cancers by next generation sequencing2022

    • Author(s)
      白石航也
    • Organizer
      日本癌学会
    • Related Report
      2022 Annual Research Report

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Published: 2021-07-13   Modified: 2024-01-30  

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