Discovery of new immune targets and development of treatments for refractory pediatric solid tumors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16404
• 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, 助教 (40771019)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経芽腫 / 腫瘍浸潤リンパ球 / 免疫チェックポイント

Outline of Final Research Achievements

We evaluated the expression of CD200 in biopsy or resection specimens of neuroblastoma, and examined its clinical significance. There were 47 specimens from patients before chemotherapy, and 25of these (53%) had high CD200 expression, while 22 had low expression. There were 28 stage 4 cases, of which 20 (80%) had high CD200 expression. The high CD200 expression group had significantly lower survival rates and recurrence-free survival rates. Furthermore, in an evaluation of 25 cases after chemotherapy, 6 cases (24%) had high CD200 expression, and the survival rate was significantly lower than in the low CD200 expression group (P = 0.007). CD200 expression in neuroblastoma is associated with prognosis, and it is possible that CD200 is associated with chemotherapy resistance.

Free Research Field

小児腫瘍

Academic Significance and Societal Importance of the Research Achievements

神経芽腫におけるT細胞抑制分子発現の臨床学的意義を検討した。神経芽腫では腫瘍浸潤リンパ球が少ないことが、免疫治療の効果が限定的になる要因として考えられている。そこで今回はさまざまな腫瘍細胞上に発現しT細胞抑制分子として知られているCD200に着目した。CD200はT細胞の腫瘍浸潤を阻害しているとされ、CD200を治療法的にすることは腫瘍浸潤リンパ球の促進と免疫チェックポイント阻害の双方の作用から神経芽腫において高い治療効果が得られる可能性がある。今回の検討からCD200発現は予後と化学療法抵抗性に関連しており、化学療法抵抗性難治症例における新規治療標的としての可能性がある。