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Analysis of interaction between gastric cancer cells and immune cells in Epstein-Barr virus associated gastric carcinoma

Research Project

Project/Area Number 18K07012
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Abe Hiroyuki  東京大学, 大学院医学系研究科(医学部), 講師 (40708632)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords胃癌 / 食道癌 / 腫瘍免疫 / Epstein-Barr virus / 神経内分泌細胞癌 / PD-L1 / EBV / 炎症細胞 / 免疫組織化学 / 神経内分泌癌
Outline of Final Research Achievements

I analyzed tumor immune status in Epstein-Barr virus associated gastric cancer (EBVaGC) and neuroendocrine carcinoma (NEC). In EBVaGC, high viral copy number in a single tumor cell was associated with poor prognosis and frequent PD-L1 expression. Viral copy number is thought to be an important factor for tumor immune evasion in EBVaGC. However, in peritoneal dissemination of EBVaGC, the number of CD8-positive cells infiltrating in the tumor was small compared to the primary tumor, although the number of cases analyzed was small. Use of immune checkpoint therapy should be considered carefully in cases with peritoneal disseminations. Neuroendocrine carcinoma in the stomach and esophagus expressed PD-L1 in 60% to 70% cases. PD-1/PD-L1 pathway was thought as a potential therapeutic target in gastric and esophageal NEC.

Academic Significance and Societal Importance of the Research Achievements

ウイルス感染を特徴とするEpstein-Barr virus関連胃癌(EBV胃癌)、及び予後不良で有効な治療標的が確立されていない神経内分泌細胞癌(Neuroendocrine carcinoma, NEC)を対象に、腫瘍免疫状態の解析を行った。その結果、EBV胃癌での腫瘍細胞内ウイルス量とPD-L1(腫瘍免疫回避に重要な分子)の発現が相関することが分かり、腫瘍免疫回避機構の一端を明らかにすることができた。また胃や食道に発生するNECは高頻度にPD-L1を発現しており、PD-L1が治療標的となり得ることが明らかとなった。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma2020

    • Author(s)
      Yamashita Satoshi、Abe Hiroyuki、Kunita Akiko、Yamashita Hiroharu、Seto Yasuyuki、Ushiku Tetsuo
    • Journal Title

      Histopathology

      Volume: 78 Issue: 3 Pages: 381-391

    • DOI

      10.1111/his.14230

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein?Barr Virus-associated gastric carcinoma2019

    • Author(s)
      Nakayama Atsuhito、Abe Hiroyuki、Kunita Akiko、Saito Ruri、Kanda Teru、Yamashita Hiroharu、Seto Yasuyuki、Ishikawa Shumpei、Fukayama Masashi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0211358-e0211358

    • DOI

      10.1371/journal.pone.0211358

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extranodal NK/T-cell lymphoma of the nasal cavity developed in a patient with intestinal Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorder.2018

    • Author(s)
      Furuya G, Abe H, Shinozaki-Ushiku A, Yamashita A, Ihara S, Hirata Y, Chiba A, Fujioka Y, Kurokawa M, Koike K, Fukayama M.
    • Journal Title

      Pathol Res Pract

      Volume: 214 Issue: 7 Pages: 1051-1055

    • DOI

      10.1016/j.prp.2018.05.022

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD47 expression in Epstein-Barr virus-associated gastric carcinoma: coexistence with tumor immunity lowering the ratio of CD8+/Foxp3+ T cells2018

    • Author(s)
      Abe Hiroyuki、Saito Ruri、Ichimura Takashi、Iwasaki Akiko、Yamazawa Sho、Shinozaki-Ushiku Aya、Morikawa Teppei、Ushiku Tetsuo、Yamashita Hiroharu、Seto Yasuyuki、Fukayama Masashi
    • Journal Title

      Virchows archiv

      Volume: 印刷中 Issue: 4 Pages: 643-651

    • DOI

      10.1007/s00428-018-2332-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 胃内分泌細胞癌における治療標的分子発現2020

    • Author(s)
      山下智,阿部浩幸,山下裕玄,瀬戸泰之,牛久哲男
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胃癌背景粘膜におけるARID1A及びp53の発現異常と遺伝子変異2019

    • Author(s)
      阿部浩幸、六反啓文、十時泰、牛久哲男、柴田龍弘、深山正久
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 胃癌組織におけるEZH2の臨床病理学的意義およびARID1A、BAP1との関係について2018

    • Author(s)
      大井手 慶、阿部 浩幸、山澤 翔、牛久 哲男、深山 正久
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] バレット食道の表在腺癌におけるp53、ARID1A、EZH2の免疫組織学的発現検討2018

    • Author(s)
      阿部 浩幸、深山 正久、Vieth Michael
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] EBV関連胃癌におけるウイルスコピー数とその臨床病理学的意義2018

    • Author(s)
      中山敦仁、阿部浩幸、国田朱子、深山正久
    • Organizer
      第15回EBウイルス研究会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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