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Clinicopathological analysis of EBV-positive B-cell lymphoproliferative disorders especially addressed on microenvironmental immune cell signatures

Research Project

Project/Area Number 19K16597
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Kato Seiichi  愛知県がんセンター(研究所), 個別化医療TR分野, 研究員 (30584669)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
KeywordsEpstein-Barr virus (EBV) / 加齢性EBV関連B細胞リンパ増殖異常症 / 医原性免疫不全関連リンパ増殖異常症 / 免疫微小環境 / EBV / 医原性免疫不全関連B細胞リンパ増殖異常症
Outline of Research at the Start

加齢性EBウイルス(EBV)関連B細胞リンパ増殖異常症(AR-EBVLPD)は、高齢者において発症する予後不良なリンパ増殖性疾患です。免疫老化・加齢に伴う免疫不全が病因として推定されていますが、発症メカニズムは不明です。本研究ではAR-EBVLPDについて、免疫微小環境等が、免疫不全関連リンパ増殖異常症(I-EBVLPD)やEBV陰性びまん性大細胞型B細胞リンパ腫とどのように異なるかを中心に解析を行います。これらの解析により特にAR-EBVLPDやI-EBVLPDの発症に関連する分子病態の解明を目指します。

Outline of Final Research Achievements

In order to clarify the characteristics of the microenvironmental profile of age-related EBV-associated B-cell lymphoproliferative disorders (EBVBLPD), nCounter analysis was performed to compare the immune microenvironmental expression profile of cases of age-related EBVBLPD with that of methotrexate(MTX)-related EBVLPD cases showing spontaneous remission by MTX withdrawal.
In the clustering analysis, both cases were mixed and did not form independent clusters, suggesting that they may be similar in terms of immune microenvironment profile. However, some genes whose expression levels were significantly different by more than 2 times were found, further investigation is required.

Academic Significance and Societal Importance of the Research Achievements

加齢性EBV関連B細胞リンパ増殖異常症(AR-EBVLPD)は予後不良であるが発症メカニズムは不明である。我々はEBVLPDではあるもののメソトレキセートの投与歴がありその休薬のみにより自然寛解した医原性免疫不全関連EBVBLPDと、その免疫微小環境プロファイルを比較検討した。不十分な症例数であるがクラスタリング解析では両症例は混在し独立したクラスターを形成せず、免疫微小環境プロファイル上は両疾患類似している可能性等示唆された。ただ両症例群で2倍以上有意に発現量に差のあった遺伝子がいくつか見つかり、AR-EBVLPDを特徴づける分子機構を反映している可能性があり、さらなる解析が必要である。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (1 results)

  • [Journal Article] Expression of programmed cell death ligand‐1 by immune cells in the microenvironment is a favorable prognostic factor for primary diffuse large B‐cell lymphoma of the central nervous system2020

    • Author(s)
      Tsuyuki Yuta、Ishikawa Eri、Kohno Kei、Shimada Kazuyuki、Ohka Fumiharu、Suzuki Yuka、Mabuchi Seiyo、Satou Akira、Takahara Taishi、Kato Seiichi、Miyagi Shohei、Ozawa Hiroyuki、Kawano Tasuku、Takagi Yusuke、Hiraga Junji、Wakabayashi Toshihiko、Nakamura Shigeo
    • Journal Title

      Neuropathology

      Volume: 41 Issue: 2 Pages: 99-108

    • DOI

      10.1111/neup.12705

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reappraisal of Primary Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract2020

    • Author(s)
      Miyagi Shouhei、Ishikawa Eri、Nakamura Masanao、Shimada Kazuyuki、Yamamura Takeshi、Furukawa Kazuhiro、Tanaka Tsutomu、Mabuchi Seiyo、Tsuyuki Yuta、Kohno Kei、Sakakibara Ayako、Satou Akira、Kato Seiichi、Fujishiro Mitsuhiro、Nakamura Shigeo
    • Journal Title

      American Journal of Surgical Pathology

      Volume: 44 Issue: 9 Pages: 1173-1183

    • DOI

      10.1097/pas.0000000000001499

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analysis of neoplastic PD-L1-positive EBV+ diffuse large B cell lymphoma, not otherwise specified, in a Japanese cohort2020

    • Author(s)
      Takahara Taishi、Satou Akira、Ishikawa Eri、Kohno Kei、Kato Seiichi、Suzuki Yuka、Takahashi Emiko、Ohashi Akiko、Asano Naoko、Tsuzuki Toyonori、Nakamura Shigeo
    • Journal Title

      Virchows Archiv

      Volume: 478 Issue: 3 Pages: 541-552

    • DOI

      10.1007/s00428-020-02901-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical Assessment of the Diagnostic Utility of PD-L1 (Clone SP142) for Methotrexate-Associated Lymphoproliferative Disorders With an Emphasis of Neoplastic PD-L1 (Clone SP142)?Positive Classic Hodgkin Lymphoma Type2020

    • Author(s)
      Kohno Kei、Suzuki Yuka、Elsayed Ahmed A、Sakakibara Ayako、Takahara Taishi、Satou Akira、Kato Seiichi、Nakamura Shigeo、Asano Naoko
    • Journal Title

      American Journal of Clinical Pathology

      Volume: 153 Issue: 5 Pages: 571-582

    • DOI

      10.1093/ajcp/aqz198

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] EBV関連リンパ増殖異常症の鑑別と病理 B細胞リンパ増殖性疾患を中心に2020

    • Author(s)
      加藤省一
    • Organizer
      第23回日本血液病理研究会
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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