Influence of Glioblastoma stem cells to the escape phenomenon in immunotherapy including WT1 vaccination

2015 Fiscal Year Final Research Report

• Project/Area Number: 24592160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Osaka University
• Principal Investigator: KAGAWA Naoki 大阪大学, 医学(系)研究科(研究院), 助教 (50444542)
• Co-Investigator(Kenkyū-buntansha): HOSEN Naoki 大阪大学, 大学院医学系研究科・寄附講座, 准教授 (10456923) ; HASHIMOTO Naoya 京都府立医科大学, 大学院医学系研究科, 准教授 (90315945)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: WT1 / ALCAM / 主要幹細胞 / 腫瘍内免疫

Outline of Final Research Achievements

We found activated leukocyte cell adhesion molecule (ALCAM) was highly expressed on glioblastoma progenitor cells and ALCAM and its soluble isoform were involved in glioblastoma invasion, progression and angiogenesis. About IDH1-R132H-positve gliomas, the frequency of ALCAM-positive cells was significantly higher in WHO grade IV than in II or III. In primary glioblastomas, median PFS and OS for the patients with high percentage of positive cells was significantly worse. Group showing periventricular origin at initial diagnosis and/or diffuse invasive recurrence more highly expressed ALCAM, compared with others.
We have also shown that the escape phenomena from WT1 vaccination was in part due to a decrease of WT1/HLA class I molecule expression and increase of Treg in tumor microenvironment. ALCAM may influence the escape phenomenon inducing Treg invasion in GBM.

Free Research Field

悪性脳腫瘍、主要幹細胞、腫瘍免疫