Cancer cell reprogramming targeting immune checkpoint in brain tumors
| Project/Area Number |
18K09001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Kyoto Prefectural University of Medicine |
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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)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(24 results)
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[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
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Journal Title
PLoS One
Volume: 15(2)
Issue: 2
Pages: e0229577-e0229577
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Sci Rep
Volume: 9(1)
Issue: 1
Pages: 10004-10004
DOI
Related Report
Peer Reviewed / Open Access
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[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
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