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Cancer cell reprogramming targeting immune checkpoint in brain tumors

Research Project

Project/Area Number 18K09001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Takashima Yasuo  京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (50621083)

Co-Investigator(Kenkyū-buntansha) 山中 龍也  京都府立医科大学, 医学部, 特任教授 (20323991)
川口 淳  佐賀大学, 医学部, 教授 (60389319)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords中枢神経系原発リンパ腫 / エクソーム / トランスクリプトーム / メタボローム / がん免疫 / マイクロRNA / 膠芽腫 / グリオーマ幹細胞 / エクソーム解析 / マイクロRNAアレイ / 網羅的N型糖鎖発現解析 / メタボローム解析 / N型糖鎖 / 間葉系幹細胞 / 多変量解析 / PD-1 / がん細胞リプログラミング / 分子標的治療薬 / 免疫チェックポイント / がん幹細胞 / 脳リンパ腫 / 神経膠腫
Outline of Final Research Achievements

Exon-mutations and expression changes of cancer immunity genes associated with poor prognoses were found in primary central nervous system lymphoma (PCNSL). Prognosis prediction in PCNSL enables by expression changes of miR-101/548b/554/1202. In methotrexate (MTX)-resistant PCNSL cell lines, cell-type-specific increased glycolysis and high-mannose and decreased sialylated A2G2F and A2G2FB were found. Bortezomib increased MTX sensitivities in PCNSL. While, in glioblastoma, expression changes of B7-H3, GATA3, and LGALS on immune checkpoint pathway could also predict prognoses. In addition, expression of mesenchymal and glioma stem cell genes enables prognosis predictions.

Academic Significance and Societal Importance of the Research Achievements

本研究では、中枢神経系原発悪性リンパ腫および膠芽腫におけるトランスクリプトーム、マイクロRNAアレイ、プロテオーム、メタボローム、網羅的N型糖鎖発現、レクチンアレイのデータを取得し、がん免疫や微小環境に関わるマイクロRNAを含む複数のリプログラミング因子の候補を得た。さらに候補因子を絞り込み、これらの腫瘍細胞においてリプログラミングを行うことで正常細胞へと誘導できる可能性がある。これは、これまでの外科治療、化学療法、放射線治療、がん免疫療法に続く次世代型がん治療再生医療へと発展する可能性がある。

Report

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

    (24 results)

All 2021 2020 2019 2018 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma2021

    • Author(s)
      Yasuo Takashima, Atsushi Kawaguchi, Junya Fukai, Yasuo Iwadate, Koji Kajiwara, Hiroaki Hondoh, Ryuya Yamanaka
    • Journal Title

      PLoS One

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL2020

    • Author(s)
      Takashima Y, Hamano M, Fukai J, Iwadate Y, Kajiwara K, Kobayashi T, Hondoh H, Yamanaka R.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 8435-8435

    • DOI

      10.1038/s41598-020-65463-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 中枢神経系原発悪性リンパ腫のがん細胞ダイレクトリプログラミング候補因子の同定2020

    • Author(s)
      高島康郎, 山中龍也
    • Journal Title

      メディカル・サイエンス・ダイジェスト

      Volume: 46 Pages: 52-53

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 中枢神経系原発悪性リンパ腫における予後予測因子の次世代がん治療再生医療への応用2020

    • Author(s)
      高島 康郎, 山中 龍也
    • Journal Title

      プレシジョン・メディシン

      Volume: 3 Pages: 47-48

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Metabolome Analysis Reveals Excessive Glycolysis via PI3K/AKT/mTOR and RAS/MAPK Signaling in Methotrexate-Resistant Primary CNS Lymphoma-Derived Cells2020

    • Author(s)
      Takashima Y, Hayano A, Yamanaka R
    • Journal Title

      Clin Cancer Res

      Volume: - Pages: 2754-2766

    • DOI

      10.1158/1078-0432.ccr-18-3851

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma2020

    • Author(s)
      Takashima Y, Kawaguchi A, Iwadate Y, Hondoh H, Fukai J, Kajiwara K, Hayano A, Yamanaka R
    • Journal Title

      PLoS One

      Volume: 15(2) Issue: 2 Pages: e0229577-e0229577

    • DOI

      10.1371/journal.pone.0229577

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promising Prognosis Marker Candidates on the Status of Epithelial-Mesenchymal Transition and Glioma Stem Cells in Glioblastoma2019

    • Author(s)
      Takashima Y, Kawaguchi A, Yamanaka R
    • Journal Title

      Cells

      Volume: 8(11) Issue: 11 Pages: 1312-1312

    • DOI

      10.3390/cells8111312

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential expression of N-linked oligosaccharides in methotrexate-resistant primary central nervous system lymphoma cells2019

    • Author(s)
      Takashima Y, Yoshimura T, Kano Y, Hayano A, Hondoh H, Ikenaka K, Yamanaka R
    • Journal Title

      BMC Cancer

      Volume: 19(1) Issue: 1 Pages: 910-910

    • DOI

      10.1186/s12885-019-6129-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL2019

    • Author(s)
      Takashima Y, Kawaguchi A, Sato R, Yoshida K, Hayano A, Homma J, Fukai J, Iwadate Y, Kajiwara K, Ishizawa S, Hondoh H, Nakano M, Ogawa S, Tashiro K, Yamanaka R
    • Journal Title

      Sci Rep

      Volume: 9(1) Issue: 1 Pages: 10004-10004

    • DOI

      10.1038/s41598-019-46473-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme2019

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 5 Pages: e0216825-e0216825

    • DOI

      10.1371/journal.pone.0216825

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-type specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells2019

    • Author(s)
      Hayano Azusa、Takashima Yasuo、Yamanaka Ryuya
    • Journal Title

      International Journal of Clinical Oncology

      Volume: April Issue: 9 Pages: 1020-1029

    • DOI

      10.1007/s10147-019-01451-9

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma2019

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Iwadate Yasuo、Hondoh Hiroaki、Fukai Junya、Kajiwara Koji、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210400-e0210400

    • DOI

      10.1371/journal.pone.0210400

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors2018

    • Author(s)
      Takashima Yasuo、Horisawa Kenichi、Udono Miyako、Ohkawa Yasuyuki、Suzuki Atsushi
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 11 Pages: 3543-3553

    • DOI

      10.1111/cas.13798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The expression of PD-1 ligands and IDO1 by macrophage/microglia in primary central nervous system lymphoma2018

    • Author(s)
      Miyasato Yuko、Takashima Yasuo、Takeya Hiroto、Yano Hiromu、Hayano Azusa、Nakagawa Takenobu、Makino Keishi、Takeya Motohiro、Yamanaka Ryuya、Komohara Yoshihiro
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 58 Issue: 2 Pages: 95-101

    • DOI

      10.3960/jslrt.18001

    • NAID

      130007403913

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Target amplicon exome-sequencing identifies promising diagnosis and prognostic markers involved in RTK-RAS and PI3K-AKT signaling as central oncopathways in primary central nervous system lymphoma2018

    • Author(s)
      Takashima Yasuo、Sasaki Yasushi、Hayano Azusa、Homma Jumpei、Fukai Junya、Iwadate Yasuo、Kajiwara Koji、Ishizawa Shin、Hondoh Hiroaki、Tokino Takashi、Yamanaka Ryuya
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 44 Pages: 27471-27486

    • DOI

      10.18632/oncotarget.25463

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma2018

    • Author(s)
      Takashima Yasuo、Kawaguchi Atsushi、Kanayama Tomohiko、Hayano Azusa、Yamanaka Ryuya
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 27 Pages: 19065-19078

    • DOI

      10.18632/oncotarget.24897

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Excessive glycolysis with mTOR and hypoxia signaling pathways in methotrexate-resistant primary CNS lymphoma cells2020

    • Author(s)
      Yasuo Takashima, Azusa Hayano, Ryuya Yamanaka
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 膠芽腫における上皮間葉転換およびグリオーマ幹細胞に関する遺伝子発現による予後予測2020

    • Author(s)
      高島康郎, 川口淳, 山中龍也
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 中枢神経系原発悪性リンパ腫におけるTh1/Th2バランスとPD-1およびPD-L2遺伝子発現による予後予測2019

    • Author(s)
      高島 康郎、川口 淳、佐藤 隆一、吉田 健一、早野 あづさ、本間 順平、深井 順也、岩立 康男、梶原 浩司、石澤 伸、本道 洋昭、中野 正和、小川 誠司、田代 啓、山中 龍也
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] The miRNA signature constituted of miR-30d, miR-93, and miR-181b as promising prognostic markers in primary CNS lymphoma2019

    • Author(s)
      Yasuo Takashima, Atsushi Kawaguchi, Yasuo Iwadate, Hiroaki Hondoh, Junya Fukai, Koji Kajiwara, Azusa Hayano, Ryuya Yamanaka
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of molecular marker candidate by Ion Reporter exome sequencing in primary central nervous system lymphoma2018

    • Author(s)
      Yasuo Takashima, Yasushi Sasaki, Azusa Hayano, Jumpei Homma, Junya Fukai, Yasuo Iwadate, Koji Kajiwara, Shin Ishizawa, Hiroaki Hondoh, Takashi Tokino, Ryuya Yamanaka
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Establishment of methotrexate-resistant primary central nervous system lymphoma cell lines and sensitivity to bortezomib2018

    • Author(s)
      Azusa Hayano, Yasuo Takashima and Ryuya Yamanaka
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Expression analysis of N-oligosaccharides of glycoproteins in methotrexate-resistant central nervous system lymphoma cell lines2018

    • Author(s)
      Yasuo Takashima, Takeshi Yoshimura, Yuichiro Kano, Azusa Hayano, Hiroaki Hondoh, Kazuhiro Ikenaka, Ryuya Yamanaka
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 京都府立医科大学報道発表【論文掲載】

    • URL

      https://www.kpu-m.ac.jp/doc/news/2020/20200304.html

    • Related Report
      2019 Research-status Report

URL: 

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

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