Basic research for the development of antitumor immunotherapy for neuroblastoma using immune checkpoint inhibition

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Saitama Medical University
• Principal Investigator: Seiichiro Inoue 埼玉医科大学, 医学部, 准教授 (70431690)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: neuroblastoma / 免疫チェックポイント阻害 / dendritic cell

Outline of Final Research Achievements

The effect of immune checkpoint inhibitor on mouse neuroblastoma was investigated and host immune cells were analyzed in the tumor microenvironment. Neuro-2a cells were inoculated subcutaneously into mice, followed by intraperitoneal injection of antibodies targeting PD-1 and PD-L1. Tumor-infiltrating cells were analyzed. Growth of subcutaneous tumors was significantly suppressed, and PD-L1-expressing tumor cells were depleted by the antibody treatment. Neuro-2a cells opsonized by the anti-PD-L1 antibody were phagocytosed in the in vitro setting. In the treated tumor microenvironments, CD8+ lymphocyte and CD11c+ MHC II+ cells were accumulated. Immune suppressive effects of CD11b+Gr-1+ myeloid-derived suppressor cells by the administration of anti-PD-1 and PD-L1 antibodies were not observed. The possibility that co-administration of anti-PD-1 and anti-PD-L1 antibodies have a synergistic effect on inhibition of tumor growth and could be an effective therapy against neuroblastoma.

Free Research Field

小児外科学

Academic Significance and Societal Importance of the Research Achievements

難治性進行小児神経芽腫に対する新たな免疫療法として、抗PD-1抗体PD-L1抗体の同時投与は抗腫瘍効果を示すことを確認し、pre clinical dataとして提供することができた。さらにこの抗体治療の効果のメカニズムには腫瘍に浸潤するリンパ球と貪食細胞が関与し、Antigen dependent cell phagocytosisの効果が有効に働いていることが示唆された。これらの結果は神経芽腫に対する新たな免疫治療の可能性を提示しながら、さらに腫瘍免疫学という基礎医学領域における新たな知見を示すことができた。これは腫瘍免疫学に関する発展に大きく貢献できる可能性があり意義が大きい。