The mechanism by which anti-tumor effect by sphingomyelin deficiency and its application to tumor medication.

• Project/Area Number: 18H02697
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Ishikawa Prefectural University (2019-2020); Kanazawa Medical University (2018)
• Principal Investigator: Okazaki Toshiro 石川県立大学, 生物資源環境学部, 客員教授 (40233308)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: スフィンゴミエリン合成酵素 / セラミドスフィンゴミエリン / 腫瘍免疫 / ミクロドメイン / セラミド / スフィンゴミエリン / 白血病 / スフィンゴ脂質 / 治療 / マウスモデル / ＳＭＳ２

Outline of Final Research Achievements

_In mouse immune-competent AML model the activation of anti-tumor immunity by anti-PD1 antibody was not shown. Therefore, anti-tumor immunity shown in SMS2-KO mice is different from the known anti-tumor immunity by PD-1/PDL1 axis. By understanding the mechanisms by which SMS2-deficiency induces anti-tumor immunity to AML the novel anti-tumor therapy to cancer which shows the resistant to PD1-inhibiting medication, suggesting that the development of SMS2 inhibition way becomes very valuable clinically and important medically to find a novel tumor immunity-activation medicine.

Academic Significance and Societal Importance of the Research Achievements

申請者が開発した免疫応答性マウスAMLモデルでは、抗PD-1抗体投与は腫瘍抑制効果を示さない。従って、SMS2欠損を介した腫瘍抑制は、既存の免疫チェックポイント療法とは異なる新規免疫活性化機構であり、SMS2欠損を介した腫瘍免疫活性化によるAMLマウスの長期生存の分子機構を解明することで、抗PD-1抗体療法に無効の腫瘍に対して、SMS2阻害免疫療法が有効と考えられ、SMS2阻害剤の開発を目指す研究は学術的、医学的にも非常に意義深い。