Inflammasome in undifferentiated pleomorphic sarcoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16173
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: University of Fukui
• Principal Investigator: FUKUSHIMA Mana 福井大学, 学術研究院医学系部門, 准教授 (70546225)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: インフラマソーム / 軟部腫瘍 / 炎症

Outline of Final Research Achievements

Inflammasome influences both immune response and tumor microenvironment. We examined whether inflammasome functions in tumor growth or tumor suppression in undifferentiated pleomorphic sarcoma (UPS) and atypical fibroxanthoma (AFX) by using immunohistochemistry with NF-kB, NLRP3, and ASC antibodies. We scored the intensity of each staining on respective tumor cells and stromal lymphocytes/histiocytes and compared their expression scores in each population.
The results showed that the NLRP3 inflammasome was significantly activated in both tumor cells and stromal lymphocytes/histiocytes in UPS compared to AFX. Moreover, the nuclear positivity of NF-kB was also seen in all the cases examined, suggesting that NF-kB activation may play an important role in NLRP3 inflammasome activation in UPS. (manuscript in preparation)

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

NLRP3インフラマソームは炎症を惹起して様々な危険因子から生体を防御する機構であるが，腫瘍においては腫瘍増殖に働く場合と増殖抑制に働く場合があるとされる．今回我々は，形態学的に類似する未分化多形肉腫（UPS）と皮膚異型線維黄色腫（AFX）におけるNLRP3インフラマソームを比較し，UPSにおいてNLRP3インフラマソームが有意に活性化されていることを見出した．UPSはAFXに比べて予後が悪い．インフラマソームの活性化の違いが予後に影響している可能性が示された．またインフラマソームの関与が明らかとなれば，インフラマソームを抑える薬を選択するなど今後の軟部腫瘍治療に貢献できることが期待される．