Relationship between immune response in therapies for malignant glioma and tymor heterogeneity

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09457
• 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: Osaka University
• Principal Investigator: Naoki Kagawa 大阪大学, 大学院医学系研究科, 講師 (50444542)
• Co-Investigator(Kenkyū-buntansha): 坪井 昭博 大阪大学, 大学院医学系研究科, 招へい教授 (10372608)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 悪性神経膠腫 / 免疫応答 / heterogeneity / 腫瘍幹細胞 / 腫瘍血管正常化

Outline of Final Research Achievements

We showed the signaling pathway mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function and improve drug delivery in xenograft model of glioblastomas. LPA4 promotes fine vascular formation and induces functional vasculature in malignant brain tumors.
LPA4 injection resulted in increased tumor-infiltrating lymphocytes in brain tumors. LPA4 improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti-programmed cell death-1 antibody therapy. A combination of LPA4 and anti-PD-1 antibody extended median survival relative to the single-agent anti-PD-1 antibody. LPA4 enhanced the anticancer effect of anti-PD-1 antibody therapy.

Free Research Field

脳腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年急速に解明が進んでいる神経膠腫のゲノム異常と分子分類による予後予測に加えて、腫瘍幹細胞や微小環境による腫瘍免疫抑制の解明、免疫療法（ワクチンや細胞療法）と新生血管抑制因子を含む分子標的薬との組み合わせやタイミングなどを模索することにより、我が国発信の免疫療法を含んだ新たな臨床試験の可能性が広がり、治療成績を改善させる礎となることを期待するものである。