Assessment of immune resistant mechanism in malignant glioma

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: Ohno Makoto 国立研究開発法人国立がん研究センター, 中央病院, 医員 (70598648)
• Co-Investigator(Kenkyū-buntansha): 北野 滋久 公益財団法人がん研究会, 有明病院 がん免疫治療開発部, 部長 (60402682) ; 吉田 朗彦 国立研究開発法人国立がん研究センター, 中央病院, 医員 (80574780) ; 里見 介史 国立研究開発法人国立がん研究センター, 中央病院, 医員 (10633977)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 悪性神経膠腫 / 免疫逃避機序 / PD-L1 / リンパ球 / マクロファージ / MGMT / IDH1/2

Outline of Final Research Achievements

We analyzed PD-L1 (Programmed cell death ligand -1) and various tumor infiltrating lymphocytes (CD4+, CD8+) and macrophages (CD68+, CD204+) immunohistochemically in 71 samples of patients with newly diagnosed malignant glioma. PD-L1 expression was observed in 21.1% of 71 samples. CD4+ and CD8+ cells were significantly associated with PD-L1 expression but not with IDH (isocitrate dehydrogenase) 1/2 mutation status and MGMT (O-6-methylguanine DNA methyltransferase) promoter methylation status. Among 44 patients with glioblastoma, IDH-wildtype, PD-L1+/immune cell+ group consisted of 10 cases (22.7%), whose median overall survival (MST) was 21.3 months. PD-L1-/immune cell+ group consisted of 20 cases (45.5%), and the MST was 12.5 months, which was shorter than that of PD-L1+/immune cell+ group. This study might contribute to develop new therapeutic approaches according to the different immune resistant mechanism.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義として悪性神経膠腫におけるPD-L1発現、腫瘍内浸潤リンパ球、マクロファージ、悪性神経膠腫の遺伝子変異との関係を検討し、悪性神経膠腫をPD-L1発現と免疫細胞浸潤有無により分類し、その割合と予後を明らかにしたことが挙げられる。PD-L1発現と免疫細胞浸潤有無により異なる免疫逃避機序を理解することで、悪性神経膠腫における免疫逃避機序を標的とした治療開発の基盤となり治療効果を予測するバイオマーカーの同定に寄与できることが期待できる。