Investigation in acquired immune system of pediatric solid tumor

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18068
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Zuo Shogo 奈良県立医科大学, 医学部附属病院, 研究員 (40771019)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 免疫チェックポイント阻害剤 / 腫瘍免疫 / 神経芽腫

Outline of Final Research Achievements

The PD-1/PD-L1 pathway has garnered much attention for its roles in clinical oncology. We evaluated the PD-L1 expression and TIL status in 31 patients with neuroblastoma who underwent a biopsy or resection by an immunohistochemical analysis. Furthermore, we performed the serial analysis of the PD-L1 status before and after chemotherapy in 15 patients.Among the 31 cases, 11 (35%) showed a positive PD-L1 expression. The survival analysis showed a trend toward an association between PD-L1 positivity and a decreased overall survival. In the serial analysis of the PD-L1 status, positivity was noted in 8 of 15 patients before chemotherapy and 6 after chemotherapy. Notably, all four patients with a positive PD-L1 status both before and after chemotherapy had recurrence, and three of them died during the follow-up period. Our findings suggest that the PD-L1 tumor expression might be a good biomarker for the treatment of neuroblastoma patients, especially for advanced neuroblastoma.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

小児固形癌は診断時に遠隔転移を認める症例が多く、このようなハイリスク患者の予後は依然不良である。また、長期生存例においても化学療法や手術治療に伴う合併症、後遺症の影響が問題となる。成人癌の分野で新規治療法として注目されている免疫チェックポイント阻害剤はすでに臨床応用され、その効果が報告されているが、小児がん分野での検討はいまだ少ない。小児がん患児に対し、免疫チェックポイント阻害剤の導入や新たな治療標的分子による新規治療薬の開発は、患児の予後改善や副作用軽減に寄与できる可能性がある。今回の検討から、特に現在有効な治療法のない再発例にPD-1/PD-L1経路が治療標的となりうる可能性が示された。