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Elucidation of mechanisms underlying lymphoproliferative disorders for targeted therapy in patients with autoimmune diseases

Research Project

Project/Area Number 16K08683
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionHokkaido University

Principal Investigator

Hatanaka Kanako  北海道大学, 大学病院, 特任講師 (10399834)

Co-Investigator(Kenkyū-buntansha) 畑中 豊  北海道大学, 大学病院, 特任准教授 (30589924)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsリンパ増殖性疾患 / 自己免疫性疾患 / びまん性大細胞型B細胞リンパ腫 / 腫瘍微小環境 / 自己免疫性疾患関連リンパ増殖性疾患 / DNAメチル化 / 治療効果予測 / 病理学 / 癌 / ゲノム
Outline of Final Research Achievements

In this study, we analyzed the tumor microenvironment of diffuse large B-cell lymphoma (DLBCL) in patients with autoimmune disease (AID) treated with immunosuppressants. The number of patients with increased FOXP3-positive regulatory T-cell infiltration was significantly higher in the AID group than in the non-AID (nAID) group. Gene expression profiling revealed a significant difference in 7 genes between AID and nAID groups. In addition, among the 24 differentially expressed genes between the AID group with and without EBV infection, 4 genes including TNFRSF8 (CD30) showed increased expression. These results further our understanding of the tumor microenvironment and can be useful for the development of therapeutic strategies for AID-DLBCL patients in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究ではAID-DLBCLの腫瘍微小環境に着目し、nAID-DLBCLとの比較やEBV感染の有無を含めた解析を行った。腫瘍微小環境の浸潤細胞の密度に大きな差異は認められなかったが、遺伝子発現プロファイル解析では複数の遺伝子発現に違いがみられたことから、形態的は大きな差異のない両者においても腫瘍微小環境に違いがみられることが判明し、かつその中の高発現を示す遺伝子をターゲットにした治療薬がすでに他の腫瘍で臨床導入されていることから、本疾患における新たな治療法の可能性を見出した。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(12 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Quantitative detection of IKZF1 deletion by digital PCR in patients with acute lymphoblastic leukemia2019

    • Author(s)
      Hashiguchi J, Onozawa M, Okada K, Amano T, Hatanaka KC, Nishihara H, Sato N, Teshima T
    • Journal Title

      Int J Lab Hematol.

      Volume: 41

    • DOI

      10.1111/ijlh.12945

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 胸水中にIgG4陽性形質細胞浸潤を証明できた、IgG4関連疾患と考えられる1例2018

    • Author(s)
      吹矢美佳,丸川克司,清水智宏,宮越里絵,安孫子光春,畑中佳奈子,三橋智子,松野吉宏
    • Journal Title

      日本臨床細胞学会雑誌

      Volume: 59 Pages: 50-55

    • NAID

      130006405500

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Re-infection of toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma2018

    • Author(s)
      Hashiguchi J, Onozawa M, Naka T, Hatanaka KC, Shiratori S, Sugita J, Fujimoto K, Matsuno Y, Teshima T
    • Journal Title

      Transpl Infect Dis

      Volume: 20

    • DOI

      10.1111/tid.12892

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytopathologic findings of cell block materials from the vitreous: Diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases2017

    • Author(s)
      Kanno-Okada H, Takakuwa E, Tagawa Y, Kase S, Hatanaka KC, Hatanaka Y, Namba K, Mitsuhashi T, Matsuno Y.
    • Journal Title

      Pathol Int

      Volume: 67 Pages: 342-349

    • DOI

      10.1111/pin.12551

    • NAID

      120006484244

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous panniculitis-like T-cell lymphoma with haemophagocytic syndrome during tocilizumab therapy for juvenile idiopathic arthritis2017

    • Author(s)
      Nakamura H, Sugai T, Kato M, Hatanaka KC, Atsumi T
    • Journal Title

      Clin Exp Rheumatol

      Volume: 35 Pages: 174-174

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Late-onset skin involvement on the forehead in multicentric Castleman disease2017

    • Author(s)
      Sato K, Shinkuma S, Fujimoto K, Hatanaka KC, Ujiie H, Nomura T, Fujita Y, Abe R, Matsuno Y, Shimizu H
    • Journal Title

      Int J Dermatol

      Volume: 56

    • DOI

      10.1111/ijd.13559

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diffuse large B-cell lymphoma with a bulky mass in the cranial vault2017

    • Author(s)
      Kanaya M, Endo T, Hashimoto D, Endo S, Takemura R, Okada K, Hatanaka KC, Matsuno Y, Teshima T
    • Journal Title

      Int J Hematol

      Volume: 106 Pages: 147-148

    • DOI

      10.1007/s12185-017-2229-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning for mycosis fungoides and Sezary syndrome.2016

    • Author(s)
      Shiratori S, Fujimoto K, Nishimura M, Hatanaka KC, Kosugi-Kanaya M, Okada K, Sugita J, Shigematsu A, Hashimoto D, Endo T, Kondo T, Abe R, Hashino S, Matsuno Y, Shimizu H, Teshima T.
    • Journal Title

      Hematol Oncol.

      Volume: Epub Ahead of Print Pages: 9-16

    • DOI

      10.1002/hon.2162

    • NAID

      120005981361

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A pilot study of operational tolerance with a regulatory T cell-based cell therapy in living donor liver transplantation.2016

    • Author(s)
      ①Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Bashuda H, Habu S, Demetris AJ, Okumura K
    • Journal Title

      Hepatology

      Volume: 00 Pages: 00-00

    • DOI

      10.1002/hep.28459

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 血管筋脂肪腫;結節性硬化症との関連を中心に2016

    • Author(s)
      畑中 佳奈子,宮島 直人,畑中 豊,篠原 信雄,松野 吉宏
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Presentation] 非小細胞肺癌におけるPD-L1とAKR1B10発現の関連性に関する検討2016

    • Author(s)
      桑原 健,畑中 豊,岡田 宏美,清水 知浩,奥村 麻美,平野 裕子, 畑中 佳奈子,樋田 泰浩,加賀 基知三,松野 吉宏
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Book] マントル細胞リンパ腫(「リンパ腫アトラス」第5版)2018

    • Author(s)
      畑中佳奈子、松野吉宏
    • Publisher
      株式会社文光堂
    • ISBN
      9784830604799
    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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