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Tumor microenvironment of T-cell lymphoma: approaching by single cell anaysis

Research Project

Project/Area Number 20K16206
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKurume University

Principal Investigator

Takeuchi Mai  久留米大学, 医学部, 助教 (10759666)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords悪性リンパ腫 / 未分化大細胞型リンパ腫 / 免疫微小環境 / 遺伝子発現解析 / シングルセル解析
Outline of Research at the Start

本研究はT細胞性リンパ腫の免疫微小環境を解明することを目的とする。nCounter法でがん免疫関連遺伝子の網羅的発現解析を行い、T細胞性リンパ腫に特異的に発現する免疫関連遺伝子を抽出する。続いて代表的な症例でImaging mass cytometryによるシングルセル解析を行い、抽出された特異的な遺伝子がコードするタンパクを発現する免疫細胞を同定し、腫瘍細胞や他の免疫細胞との相互作用を検討する。臨床データとの比較を行い、免疫微小環境の違いと予後との関係についても検討する。このことによりT細胞性リンパ腫のがん免疫治療でターゲットにするべき重要な分子を同定することを目指す。

Outline of Final Research Achievements

In this study, we investigated tumor immune microenvironment of anaplastic large cell lymphoma (ALCL), which is a type of T-cell lymphoma, using gene expression analysis by nCounter, immunostaining, and single-cell spatial analysis by Phenocycler. The results showed that CD47 and SIRPα involved in the "Don't eat me" signal were important for tumor immune microenvironment of ALCL. CD47 was expressed in ALCL tumor cells, and many SIRPα-positive stromal cells were found in the surrounding area. In conclusion, it was suggested that the immune escape mechanism by the interaction between CD47 and SIRPα may be working in ALCL.

Academic Significance and Societal Importance of the Research Achievements

T細胞性リンパ腫は化学療法の効果が不十分であり、がん免疫療法などの活用が期待される。がん免疫療法の適切な利用にはがん細胞を取り巻くT細胞などの免疫微小環境の理解が重要であるが、T細胞性リンパ腫はT細胞自体が腫瘍化しているため従来の方法では免疫微小環境の解析が困難であった。本研究では遺伝子発現解析とシングルセル解析を併用することでより詳細な検討を可能にし、治療の進歩に貢献する可能性が期待される。

Report

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

    (10 results)

All 2022 2021 2020

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (1 results)

  • [Journal Article] CD37 expression in follicular lymphoma2022

    • Author(s)
      Yoshimura T, Miyoshi H, Shimono J, Nakashima K, Takeuchi M, Yanagida E, Yamada K, Shimasaki Y, Moritsubo M, Furuta T, Kohno K, Ohshima K
    • Journal Title

      Ann Hematol

      Volume: 101 Issue: 5 Pages: 1067-1075

    • DOI

      10.1007/s00277-022-04785-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological analysis of immunohistochemical expression of immune checkpoint molecules in follicular lymphoma2022

    • Author(s)
      Yanagida E, Miyoshi H, Takeuchi T, Shimono J, Nakashima K, Yamada K, Kawamoto K, Moritsubo M, Shimasaki Y, Inoue K, Imamoto T, Furuta T, Kohno K, Ohshima K
    • Journal Title

      Hematol Oncol

      Volume: in press Issue: 4 Pages: 530-540

    • DOI

      10.1002/hon.2972

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor microenvironment of adult T-cell leukemia/lymphoma2021

    • Author(s)
      Takeuchi M, Miyoshi H, Ohshima K
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 61 Issue: 4 Pages: 202-209

    • DOI

      10.3960/jslrt.21007

    • NAID

      130008131906

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological analysis of myeloid sarcoma with megakaryocytic differentiation2021

    • Author(s)
      Nagamine M, Miyoshi H, Kawamoto K, Takeuchi M, Yamada K, Eriko Yanagida E, Kohno K, Ohshima K
    • Journal Title

      Pathology

      Volume: in press Issue: 4 Pages: 442-448

    • DOI

      10.1016/j.pathol.2021.08.015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of telomerase reverse transcriptase in peripheral T-cell lymphoma2021

    • Author(s)
      Arakawa F, Miyoshi H, Noriaki Yoshida N, Nakashima K, Watatani Y, Furuta T, Yamada K, Moritsubo M, Takeuchi M, Yanagida E, Shimasaki Y, Kohno K, Kataoka K, Ohshima K
    • Journal Title

      Cancer Med

      Volume: 10 Issue: 19 Pages: 6786-6794

    • DOI

      10.1002/cam4.4200

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human T-cell lymphotropic virus HBZ and tax mRNA expression are associated with specific clinicopathological features in adult T-cell leukemia/lymphoma2021

    • Author(s)
      Kyohei Yamada, Hiroaki Miyoshi, Noriaki Yoshida, Joji Shimono, Kensaku Sato, Kazutaka Nakashima, Mai Takeuchi
    • Journal Title

      Modern Pathology

      Volume: 34 Issue: 2 Pages: 314-326

    • DOI

      10.1038/s41379-020-00654-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive Immunohistochemical Analysis of Immune Checkpoint Molecules in Adult T Cell Leukemia/Lymphoma2020

    • Author(s)
      Takeuchi M, Miyoshi H, Nakashima T, Kawamoto K, Yamada K, Yanagida E, Muta H, Moritsubo M, Umeno T, Suzuki T, Seto M, Ohshima K.
    • Journal Title

      Annals of Hematology

      Volume: 99 Issue: 5 Pages: 1093-1098

    • DOI

      10.1007/s00277-020-03967-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of CD47 and SIRPα constituting the “don't eat me signal” is a prognostic factor in diffuse large B-cell lymphoma.2020

    • Author(s)
      Kazama R, Miyoshi H, Takeuchi M, (8名略), Kato K, Takizawa J, Seto M, Akashi K, Ohshima K.
    • Journal Title

      Cancer Sci.

      Volume: 111 Issue: 7 Pages: 2608-2619

    • DOI

      10.1111/cas.14437

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma2020

    • Author(s)
      Eriko Yanagida, Hiroaki Miyoshi, Mai Takeuchi, et al
    • Journal Title

      Hematological Oncology

      Volume: 38 Issue: 5 Pages: 680-688

    • DOI

      10.1002/hon.2768

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 成人T細胞白血病・リンパ腫における免疫チェックポイント分子の網羅的検索2020

    • Author(s)
      竹内真衣
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2023-01-30  

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