Identification of the differentiation mechanism of the immunosuppressive myeloid cells and the development of a novel virotherapy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20803
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Okayama University
• Principal Investigator: Otani Yoshihiro 岡山大学, 大学病院, 助教 (60902989)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 腫瘍溶解ウイルス療法 / NOTCH経路 / 膠芽腫 / 腫瘍微小環境

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.

Free Research Field

脳腫瘍

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。