| Project/Area Number |
18K09098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Niigata University |
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Principal Investigator |
Ogose Akira 新潟大学, 医歯学総合病院, 特任教授 (80323963)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肉腫 / 免疫環境 / 脂肪肉腫 / 免疫治療 / sarcoma / immunotherapy / HLA / macrophage / prognosis / myxoid liposarcoma / dedifferentiaion / 骨軟部肉腫 / 免疫療法 / 細胞障害性リンパ球 / Ｍ２マクロファージ / M2マクロファージ / CD8 / CD163 |
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| Outline of Final Research Achievements |
We have demonstrated that myxoid liposarcoma (MLPS) have a distinct tumor immune microenvironment from other liposarcoma subtypes. While the overall number of infiltrating TILs and macrophages in MLPS patients were significantly less than in patients with other liposarcomas, those with high macrophage numbers were shown to have poor outcome. In addition, loss or down regulation of HLA class I was frequently found in patients with MLPS. Furthermore, no patients with MLPS were positive for PD-L1, whereas about one quarter of patients with other liposarcomas were positive. Overall, the tumor immune microenvironment of the translocation-associated MLPS is markedly different from other liposarcomas suggesting that current approaches to cancer immunotherapies consisting of immunostimulatory and immunomodulatory approaches may not be as effective in MLPS compared to other subtypes of LPS.
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| Academic Significance and Societal Importance of the Research Achievements |
多形型脂肪肉腫や脱分化型脂肪肉腫ではHLA-1の発現がある程度維持され、PDL-1の発現もあるためニボルマブのような薬剤の有効性に期待が持たれる、しかし粘液型脂肪肉腫ではHLA－１の発現が著しく低下しているため現行の免疫チェックポイント阻害剤単独使用では効果が期待できないことの基礎的証明を果たした。Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas Cancer Immunology Immunotherapy に報告した。
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