Identification of the differentiation mechanism of the immunosuppressive myeloid cells and the development of a novel virotherapy.
Project/Area Number |
21K20803
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0901:Oncology and related fields
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2021-08-30 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 腫瘍溶解ウイルス療法 / NOTCH経路 / 膠芽腫 / 腫瘍微小環境 / 腫瘍溶解ヘルペスウイルス / 腫瘍溶解ウイルス / 悪性神経膠腫 / 腫瘍免疫 |
Outline of Research at the Start |
膠芽腫は予後不良であり、新規治療法の開発が急務である。腫瘍溶解ヘルペスウイルス(oncolytic HSV, oHSV)療法は、腫瘍溶解による直接的な効果に加え、抗腫瘍免疫を誘導することで治療効果を呈する新たな治療法である。 oHSV投与部に浸潤する骨髄系細胞は抗腫瘍免疫促進型および抑制型への分化を示すが、その機序は不明である。本研究では、その分化に関与する遺伝子変化を解析する。
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Outline of Final Research Achievements |
The purpose of this study was to elucidate the effect of the NOTCH pathway, which is activated by oHSV for glioblastoma. First, we examined the activation of the NOTCH pathway in glioblastoma patients and showed that immunosuppressive macrophages, M2-type macrophages, were increased in the group with high expression of NOTCH. Next, oHSV administration to a tumor-bearing mouse model showed activation of the NOTCH pathway, while the infiltration of M2 macrophages was decreased in the group treated with oHSV and NOTCH inhibitor. Through this study, we have elucidated the detailed mechanism by which the activation of the NOTCH pathway in the tumor microenvironment of glioblastoma contributes to the establishment of an immunosuppressive tumor microenvironment.
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Academic Significance and Societal Importance of the Research Achievements |
膠芽腫はもっとも予後不良な脳腫瘍の一つであり、新規治療開発は急務である。近年、ウイルス製剤を用いた治療が注目されており、とくに抗腫瘍免疫の誘導が期待されている。一方で、抗腫瘍免疫誘導の詳細な機序や、治療抵抗性機序については解明されていない。本研究では、我々が同定したNOTCH経路がoHSV投与後の抗腫瘍免疫誘導に関わる因子であることを報告し、膠芽腫の新たな治療に繋がる可能性を示した。
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Report
(3 results)
Research Products
(90 results)
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[Journal Article] Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth2023
Author(s)
Horikawa M, Koizumi S, Oishi T, Yamamoto T, Ikeno M, Ito M, Yamasaki T, Amano S, Sameshima T, Mitani Y, Otani Y, Yan Y, Suzuki T, Namba H, Kurozumi K
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Journal Title
Cancer Gene Therapy
Volume: 30
Issue: 1
Pages: 85-95
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib2022
Author(s)
Banasavadi-Siddegowda YK , Namagiri S , Otani Y , Sur H , Rivas S , Bryant JP , Shellbourn A , Rock M , Chowdhury A , Lewis CT , Shimizu T , Walbridge S , Kumarasamy S , Shah AH , Lee TJ , Maric D , Yan Y , Yoo JY , Kumbar SG , Heiss JD , Kaur B
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Journal Title
Neuro-Oncology Advances
Volume: 4(1)
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme2022
Author(s)
Arunachalam E , Rogers W , Simpson GR , Moller-Levet C , Bolton G , Ismael M , Smith C , Keegen K , Bagwan I , Brend T , Short SC , Hong B , Otani Y , Kaur B , Annels N , Morgan R , Pandha H
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Journal Title
BMC Cancer
Volume: 22(1)
Issue: 1
Pages: 400-400
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genomic Profiling of a Case of Glioneuronal Tumor with Neuropil-like Islands2022
Author(s)
Tsuboi N , Ishida J , Shimazu Y , Edaki H , Uneda A , Otani Y , Fujii K , Kurozumi K , Ennishi D , Yanai H , Date I
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Journal Title
Acta Medica Okayama
Volume: 76
Issue: 4
Pages: 473-477
DOI
URL
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration2021
Author(s)
Uneda A, Kurozumi K, Fujimura A, Fujii K, Ishida J, Shimazu Y, Otani Y, Tomita Y, Hattori Y, Matsumoto Y, Tsuboi N, Makino K, Hirano S, Kamiya A, Date I.
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Journal Title
Acta Neuropathol Commun.
Volume: 9
Issue: 1
Pages: 29-29
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma2021
Author(s)
Otani Y , Sur HP , Rachaiah G , Namagiri S , Chowdhury A , Lewis CT , Shimizu T , Gangaplara A , Wang X , Vezina A , Maric D , Jackson S, Yan Y , Zhengping Z , Ray-Chaudhury A , Kumar S , Ballester LY , Chittiboina P , Yoo JY , Heiss J , Kaur B , Banasavadi-Siddegowda YK
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Journal Title
Neuro-Oncology
Volume: 23
Issue: 9
Pages: 1481-1493
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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