2023 Fiscal Year Final Research Report
Development of a new treatment for pulmonary metastasis of osteosarcoma using a combination of inhibition of immune evasion and activation of innate immunity
| Project/Area Number |
21K09325
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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 | Fukushima Medical University (2023)
Kyushu University (2021-2022) |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 骨軟部腫瘍 / 腫瘍免疫 / 免疫逃避 / EPCAM / 細胞障害性T細胞 |
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| Outline of Final Research Achievements |
Pulmonary metastasis is the greatest factor defining the prognosis of malignant bone and soft tissue tumors, and the prognosis of metastatic cases is poor. Tumor immunotherapy has been attempted to improve prognosis, but immunotherapy has been less effective, and it was expected that bone and soft tissue tumors have some immune evasion mechanism.In this project, we investigated the differences in immune profiles between primary tumors and pulmonary metastases in malignant soft tissue tumors. As a result, it was inferred that in leiomyosarcoma, EPCAM expression was significantly upregulated in metastases, and that it was involved in immune escape by inhibiting CD8+ T cell accumulation in the tumor. Therefore, it was suggested that inhibition of EPCAM expression and function may restore tumor infiltration of CD8+ T cells and improve the prognosis of metastatic leiomyosarcoma.
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| Free Research Field |
整形外科 骨軟部腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
悪性骨軟部腫瘍の予後を規定する最大の因子は肺転移である。今回の研究により，悪性軟部腫瘍が原発巣から肺転移を来す際に、腫瘍の免疫プロファイルがどのように変化するかの詳細が明らかとなった。さらに、平滑筋肉腫における免疫逃避機構の一旦も解明した。同様の手法は他の悪性軟部腫瘍に関しても応用可能である。そのため本研究は、悪性軟部腫瘍の肺転移に対する腫瘍免疫療法の確立、ひいては予後の改善に重要であると考えられた。
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