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

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / 慢性炎症 / 脳腫瘍 / 免疫チェックポイント / B7 分子

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.

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。

Research Products

• [Journal Article] Lactobacillus reuteri DSM 17938 and Magnesium Oxide in Children with Functional Chronic Constipation: A Double-Blind and Randomized Clinical Trial (2020)
  • Author(s): Kubota M, Ito K, Tomimoto K, Kanazaki M, Tsukiyama K, Kubota A, Kuroki H, Fujita M, Vandenplas Y.
  • Journal Title: Nutrients Volume: 12 Issue: 1 Pages: 225-225
  • DOI: 10.3390/nu12010225
  • Peer Reviewed
• [Journal Article] Clinical Outcomes of Surgical Resection for Brain Metastases from Non-small Cell Lung Cancer (2020)
  • Author(s): Takayuki Nakao , Takeshi Okuda , Hiromasa Yoshioka , Mitsugu Fujita
  • Journal Title: Anticancer Res Volume: 40(8) Issue: 8 Pages: 4801-4804
  • DOI: 10.21873/anticanres.14483
  • Peer Reviewed / Open Access
• [Journal Article] Bioinformatics Analysis of Gut Microbiota and CNS Transcriptome in Virus-Induced Acute Myelitis and Chronic Inflammatory Demyelination; Potential Association of Distinct Bacteria With CNS IgA Upregulation (2020)
  • Author(s): Omura Seiichi、Sato Fumitaka、Park Ah-Mee、Fujita Mitsugu、Khadka Sundar、Nakamura Yumina、Katsuki Aoshi、Nishio Kazuto、Gavins Felicity N. E.、Tsunoda Ikuo
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 1138-1138
  • DOI: 10.3389/fimmu.2020.01138
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Galectin-3 as a Therapeutic Target for NSAID-Induced Intestinal Ulcers (2020)
  • Author(s): Park Ah-Mee、Khadka Sundar、Sato Fumitaka、Omura Seiichi、Fujita Mitsugu、Hsu Daniel K.、Liu Fu-Tong、Tsunoda Ikuo
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 550366-550366
  • DOI: 10.3389/fimmu.2020.550366
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Experimental Animal Model of Re-irradiation to Evaluate Radiation-induced Damage in the Normal Intestine (2020)
  • Author(s): Hiroshi Doi , Mikoto Tamura , Kiyoshi Nakamatsu , Hajime Monzen , Yasumasa Nishimura
  • Journal Title: Anticancer Res Volume: 40(4) Issue: 12 Pages: 1981-1988
  • DOI: 10.1038/s41417-020-00282-5
  • Peer Reviewed
• [Journal Article] Efficacy of Afatinib and Lapatinib Against HER2 Gene-amplified Trastuzumab-sensitive and -resistant Human Gastric Cancer Cells. (2019)
  • Author(s): Nakata S, Fujita M, Nakanishi H.
  • Journal Title: Anticancer Research Volume: 39 Issue: 11 Pages: 5927-5932
  • DOI: 10.21873/anticanres.13797
  • Peer Reviewed
• [Journal Article] Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8(+) Tumor-infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma. (2019)
  • Author(s): Fukuoka E, Yamashita K, Tanaka T, Sawada R, Sugita Y, Arimoto A, Fujita M, Takiguchi G, Matsuda T, Oshikiri T, Nakamura T, Suzuki S, Kakeji Y.
  • Journal Title: Anticancer Research Volume: 39 Issue: 8 Pages: 4539-4548
  • DOI: 10.21873/anticanres.13631
  • Peer Reviewed
• [Journal Article] Significance of Elevated HMGB1 Expression in Pituitary Apoplexy. (2019)
  • Author(s): Okuda T, Fujita M, Kato A.
  • Journal Title: Anticancer Research Volume: 39 Issue: 8 Pages: 4491-4494
  • DOI: 10.21873/anticanres.13624
  • Peer Reviewed
• [Journal Article] A case of leptomeningeal metastases of human epidermal growth factor receptor 2-positive breast cancer that responded well to lapatinib plus capecitabine. (2019)
  • Author(s): Nakao T, Okuda T, Fujita M, Kato A.
  • Journal Title: Surgical Neurology International Volume: 10 Pages: 131-131
  • DOI: 10.25259/sni-106-2019
  • Peer Reviewed
• [Journal Article] Basic Gene Expression Characteristics of Glioma Stem Cells and Human Glioblastoma. (2019)
  • Author(s): Sakamoto D, Takagi T, Fujita M, Omura S, Yoshida Y, Iida T, Yoshimura S.
  • Journal Title: Anticancer Research Volume: 39 Issue: 2 Pages: 597-607
  • DOI: 10.21873/anticanres.13153
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment. (2018)
  • Author(s): Yamashita K, Arimoto A, Nishi M, Tanaka T, Fujita M, Fukuoka E, Sugita Y, Nakagawa A, Hasegawa H, Suzuki S, Kakeji Y.
  • Journal Title: Anticancer Research Volume: 38 Issue: 7 Pages: 4233-4239
  • DOI: 10.21873/anticanres.12719
  • Peer Reviewed / Int'l Joint Research