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Elucidation of the molecular basis of chemokine networks and identification of potential therapeutic targets in diffuse large B-cell lymphoma associated with chronic inflammation

Research Project

Project/Area Number 20K08714
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKochi University

Principal Investigator

Daibata Masanori  高知大学, 教育研究部医療学系基礎医学部門, 教授 (50263976)

Co-Investigator(Kenkyū-buntansha) 樋口 智紀  高知大学, 教育研究部医療学系基礎医学部門, 講師 (00448771)
橋田 裕美子  高知大学, 教育研究部医療学系基礎医学部門, 助教 (00767999)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsリンパ腫 / ウイルス / ケモカイン / 慢性炎症
Outline of Research at the Start

炎症関連リンパ腫はEpstein-Barr(EB)ウイルス感染を伴うことが多く、その感染と長期的な慢性炎症がリンパ腫の発症に密接に関連する。このタイプのリンパ腫は明確な免疫不全状態にない患者においても発症することが特徴である。ケモカイン・ケモカイン受容体の網羅的発現解析やケモカイン系の腫瘍免疫回避への役割解析を行うことで、このタイプのリンパ腫に特徴的な腫瘍微小環境でのケモカインネットワークの分子基盤と免疫抑制機構を把握し、腫瘍進展メカニズムの解明に資する研究を推進する。これにより、新たな治療標的分子を同定することができ、腫瘍免疫抑制機構を破綻させることを狙った新規治療コンセプトの確立を目指す。

Outline of Final Research Achievements

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) develops in the setting of long-standing inflammation. EBV-positive pyothorax-associated lymphoma (PAL) is a prototype of DLBCL-CI. Using a panel of PAL cell lines, we found that PAL cells expressed and secreted CXCL9 and CXCL10 chemokines, the ligands of CXCR3. Culture supernatants from PAL cell lines attracted CXCR3-expressing CD4-positive T cells, CD8-positive T cells, and CD56-positive natural killer cells from human peripheral blood mononuclear cells. PAL cells injected into mice also attracted CXCR3-positive cytotoxic lymphocytes that expressed interferon-gamma. The expression of CXCL9 and CXCL10 was detected in tumor biopsy samples from patients with PAL, and CXCR3-positive lymphocytes were abundant in the tissues. Collectively, these findings suggest that CXCL9 and CXCL10 are produced by PAL cells and can elicit cytotoxic responses via CXCR3.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、PAL細胞がケモカインCXCL9とCXCL10を分泌することによりCXCR3を発現する腫瘍傷害性リンパ球を腫瘍部位に引き寄せることを示している。誘引された腫瘍傷害性リンパ球によってリンパ腫細胞を排除あるいはその進展を抑制できる可能性があり、このことを活用することにより慢性炎症に伴うびまん性大細胞型B細胞リンパ腫の新規治療法につながることが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 2020 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (12 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] Japanese Encephalitis Virus Genotypes 1 and 3 Isolation in Kochi, Japan2023

    • Author(s)
      Matsui Kiyohiko、Yamaya Miyuki、Takase Mina、Morita Koichi、Tajima Shigeru、Lim Chang-Kweng、Saijo Masayuki、Daibata Masanori、Nagayasu Seiji、Takasaki Tomohiko
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 76 Issue: 2 Pages: 151-154

    • DOI

      10.7883/yoken.JJID.2020.941

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2023-03-31
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] EBV‐positive pyothorax‐associated lymphoma expresses CXCL9 and CXCL10 chemokines that attract cytotoxic lymphocytes via CXCR32023

    • Author(s)
      Higuchi Tomonori、Hashida Yumiko、Matsuo Kazuhiko、Kitahata Kosuke、Ujihara Takako、Murakami Ichiro、Nakayama Takashi、Daibata Masanori
    • Journal Title

      Cancer Science

      Volume: - Issue: 6 Pages: 2622-2633

    • DOI

      10.1111/cas.15782

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Merkel cell polyomavirus in multiple primary oral squamous cell carcinomas2023

    • Author(s)
      Kitamura Naoya、Hashida Yumiko、Higuchi Tomonori、Ohno Seiji、Sento Shinya、Sasabe Eri、Murakami Ichiro、Yamamoto Tetsuya、Daibata Masanori
    • Journal Title

      Odontology

      Volume: - Issue: 4 Pages: 971-981

    • DOI

      10.1007/s10266-023-00807-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kimura disease forming a human polyomavirus 6-negative parotid gland nodule with prominent squamous metaplasia in a young female: A case report2023

    • Author(s)
      Yorita Kenji、Fujii Tatsuya、Nagao Toshitaka、Murakami Ichiro、Hashida Yumiko、Higuchi Tomonori、Daibata Masanori、Toi Makoto、Ayada Yoshiyuki、Igawa Takuro
    • Journal Title

      Radiology Case Reports

      Volume: 18 Issue: 5 Pages: 1933-1938

    • DOI

      10.1016/j.radcr.2023.02.027

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo2022

    • Author(s)
      Ogasawara Fumiya、Higuchi Tomonori、Nishimori Tomohiro、Hashida Yumiko、Kojima Kensuke、Daibata Masanori
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: 26 Issue: 22 Pages: 5580-5589

    • DOI

      10.1111/jcmm.17570

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histiocytosis and virus: Merkel cell polyomavirus2022

    • Author(s)
      村上 一郎、橋田 裕美子、樋口 智紀、大畑 雅典
    • Journal Title

      Rinsho Ketsueki

      Volume: 63 Issue: 5 Pages: 383-392

    • DOI

      10.11406/rinketsu.63.383

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a novel cell line‐derived xenograft model of primary herpesvirus 8‐unrelated effusion large B‐cell lymphoma and antitumor activity of birabresib in vitro and in vivo2021

    • Author(s)
      Nishimori Tomohiro、Higuchi Tomonori、Hashida Yumiko、Ujihara Takako、Taniguchi Ayuko、Ogasawara Fumiya、Kitamura Naoya、Murakami Ichiro、Kojima Kensuke、Daibata Masanori
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 24 Pages: 8976-8987

    • DOI

      10.1002/cam4.4394

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic significance of human papillomavirus 16 viral load level in patients with oropharyngeal cancer2021

    • Author(s)
      Hashida Yumiko、Higuchi Tomonori、Matsumoto Shuichi、Iguchi Mitsuko、Murakami Ichiro、Hyodo Masamitsu、Daibata Masanori
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 10 Pages: 4404-4417

    • DOI

      10.1111/cas.15105

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vertebral fracture and splenomegaly in a head and neck cancer producing granulocyte colony-stimulating factor: A case report of systemic complications associated with a cytokine-producing solid tumor2021

    • Author(s)
      Kitamura Naoya、Sento Shinya、Sasabe Eri、Kiyasu Katsuhito、Nakaji Kosuke、Daibata Masanori、Yamamoto Tetsuya
    • Journal Title

      Molecular and Clinical Oncology

      Volume: 15 Issue: 4

    • DOI

      10.3892/mco.2021.2364

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Polyomavirus 6 Detected in Cases of Eosinophilic Pustular Folliculitis.2020

    • Author(s)
      Hashida Y, Higuchi T, Nakajima S, Nakajima K, Ujihara T, Kabashima K, Sano S, Daibata M.
    • Journal Title

      Journal of Infectious Diseases

      Volume: jiaa607 Issue: 10 Pages: 1724-1732

    • DOI

      10.1093/infdis/jiaa607

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human polyomavirus 6 with the Asian/Japanese genotype in cases of Kimura disease and angiolymphoid hyperplasia with eosinophilia.2020

    • Author(s)
      Yumiko Hashida, Tomonori Higuchi, Kimiko Nakajima, Takako Ujihara, Ichiro Murakami, Mikiya Fujieda, Shigetoshi Sano, Masanori Daibata.
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 印刷中 Issue: 8 Pages: 1650-1653.e4

    • DOI

      10.1016/j.jid.2019.12.027

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Is There an Entity of Radiation-Induced Chronic Myeloid Leukemia? Report of a Case and Brief Review of the Literature2020

    • Author(s)
      Isao Miyoshi, Masakazu Mori, IchiroYamasaki, Masanori Daibata.
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 60 Issue: 1 Pages: 24-25

    • DOI

      10.3960/jslrt.19044

    • NAID

      130007821370

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Antitumor activity of birabresib in a novel xenograft model of HHV8-unrelated primary effusion lymphoma-like lymphoma.2022

    • Author(s)
      Tomonori Higuchi, Tomohiro Nishimori, Yumiko Hashida, Masanori Daibata.
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Association between HPV16 viral load and prognosis of patients with oropharyngeal squamous cell carcinoma.2022

    • Author(s)
      Yumiko Hashida, Tomonori Higuchi, Ichiro Murakami, Masamitsu Hyodo, Masanori Daibata.
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MCPyV皮膚定量により原発巣自然消退を考えたメルケル細胞癌リンパ節転移の1例.2022

    • Author(s)
      木戸一成, 角野貴應, 佐野ほづみ, 中島英貴, 橋田裕美子, 大畑雅典, 佐野栄紀.
    • Organizer
      第18回加齢皮膚医学研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] メルケル細胞ポリオーマウイルス皮膚定量により原発巣自然消退を考えたメルケル細胞癌リンパ節転移の1例.2022

    • Author(s)
      木戸一成, 角野貴應, 佐野ほづみ, 中島英貴, 橋田裕美子, 大畑雅典, 佐野栄紀.
    • Organizer
      第121回日本皮膚科学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 木村病様所見・ランゲルハンス細胞組織球症様所見を呈した一女性例:症例報告及び文献的考察・レビュー2021

    • Author(s)
      村上一郎、山鳥一郎、岩谷佳代子、表梨華、梅田直人、丸岡日向子、賴田顕辞、橋田裕美子、樋口智紀、大畑雅典
    • Organizer
      第61回日本リンパ網内系学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Histiocytosis and viral infection: Merkel cell polyomavirus, etc.2021

    • Author(s)
      Ichiro Murakami, Yumiko Hashida, Tomonori Higuchi, Masanori Daibata
    • Organizer
      第83回日本血液学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Generation and characterization of cell line-derived xenograft of HHV8-unrelated primary effusion lymphoma-like lymphoma2021

    • Author(s)
      Tomohiro Nishimori, Tomonori Higuchi, Yumiko Hashida, Masanori Daibata
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] ランゲルハンス細胞組織球症の像を伴う木村病の一例:症例報告及び文献的考察・レビュー2021

    • Author(s)
      村上一郎、山鳥一郎、岩谷佳代子、表梨華、梅田直人、丸岡日向子、賴田顕辞、林芳弘、橋田裕美子、樋口智紀、大畑雅典
    • Organizer
      第53回日本臨床分子形態学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] RNA-seq profiling in peripheral blood cells of patients with Langerhans cell histiocytosis2021

    • Author(s)
      Ichiro Murakami, Yumiko Hashida, Tomonori Higuchi, Masanori Daibata
    • Organizer
      第67回日本病理学会秋期特別総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Detection of human polyomaviruses in cases of Kimura disease and angiolymphoid hyperplasia with eosinophilia2021

    • Author(s)
      Yumiko Hashida, Tomonori Higuchi, Takako Ujihara, Masanori Daibata
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Establishment of a new cell line derived from human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma.2020

    • Author(s)
      Tomohiro Nishimori, Tomonori Higuchi, Yumiko Hashida, Ayuko Taniguchi, Kensuke Kojima, Masanori Daibata.
    • Organizer
      第79回日本癌学会学術
    • Related Report
      2020 Research-status Report
  • [Presentation] 皮膚ポリオーマウイルスのエコロジーと疾患との関わり2020

    • Author(s)
      大畑雅典
    • Organizer
      第50回日本皮膚免疫アレルギー学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] 高知大学医学部微生物学講座

    • URL

      http://www.kochi-u.ac.jp/kms/ff_mcrbi/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 高知大学医学部微生物学講座ホームページ

    • URL

      http://www.kochi-u.ac.jp/kms/ff_mcrbi/

    • Related Report
      2021 Research-status Report 2020 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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