Significance of B7 family expressed on macrophages relevant to radiation necrosis of brain

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kindai University
• Principal Investigator: FUJITA Mitsugu 近畿大学, 医学部, 准教授 (40609997)
• Co-Investigator(Kenkyū-buntansha): 中田 晋 京都薬科大学, 薬学部, 准教授 (80590695) ; 宮武 伸一 大阪医科大学, 医学部, 特別職務担当教員(教授) (90209916) ; 山下 公大 神戸大学, 医学部附属病院, 特命准教授 (80535427)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: グリオーマ / 放射線脳壊死 / マクロファージ / 免疫チェックポイント分子 / 腸内細菌叢

Outline of Final Research Achievements

In M2 macrophages accumulating in radioactive necrotic brain tissues, immunosuppressive molecules such as B7-H3 and B7-H5 were found to be upregulated. Likewise, in the mouse model, the expression of these molecules was also enhanced, and they were found to be involved in peripheral edema of radiation brain necrosis. Analysis of intestinal microflora in mice using the next generation sequencer showed that Clostridia correlated with the intensity of the immune response related to cerebral radiation necrosis. M2 removal experiment showed marked prolongation of mouse survival days. These results suggest that M2 macrophages and intestinal bacteria infiltrating into tissues are involved in the deterioration of cerebral radiation necrosis.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究結果により、脳放射線壊死巣に生じる免疫反応の詳細が明らかとなった。その実態は B7-H3 あるいは B7-H5 を発現するマクロファージによる局所的免疫抑制であり、それを適切に解除することによって発症予防あるいは治療を行いうる可能性が示唆された。これにより QOL を維持した状態でのグリオーマ治療が可能となる。