2019 Fiscal Year Final Research Report

Mechanisms of immune modulation regulated by factors from OSCC cells on the development of acquiring metastatic potential to regional lymph nodes

Research Project

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Project/Area Number	17K11891
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Surgical dentistry
Research Institution	Asahi University
Principal Investigator	Kondoh Nobuo 朝日大学, 歯学部, 教授 (40202072)
Co-Investigator(Kenkyū-buntansha)	山崎裕北海道大学, 歯学研究院, 教授 (90250464) 藤内祝横浜市立大学, 医学研究科, 客員教授 (50172127) 光藤健司横浜市立大学, 医学研究科, 教授 (70303641) 住友伸一郎朝日大学, 歯学部, 教授 (50216496) 高山英次朝日大学, 歯学部, 准教授 (70533446) 神谷真子朝日大学, 経営学部, 准教授 (80181907) 川木晴美朝日大学, 歯学部, 准教授 (70513670) 梅村直己朝日大学, 歯学部, 講師 (80609107)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	口腔扁平上皮癌 / 腫瘍微小環境 / 腫瘍関連線維芽細胞 / 腫瘍免疫
Outline of Final Research Achievements	Mouse OSCC cell line (Sq1979-1) and the subclone, L5 cells, established from metastasized lymph nodes suppressed the immunity of splenocytes of transplanted mice. Among these, Sq1979 cells promoted immunosuppressive activity of mesenchymal stromal cells (10T1 / 2) against stimulated splenocytes. This activity was mediated by IL-1α released by Sq1979 cells. IL-1α induced a class II tissue-suitable expression (H-2) gene group expressed by 10T1 / 2 cells. IL-1α expression in Sq1979 was remarkably enhanced in low serum and hypoxic conditions, resulted in enhancing the immunosuppressive effect of mesenchymal stromal cells. Our results demonstrate that, during the process of developing malignancy, OSCC exerts various immunosuppressive mechanisms in the tumor tissue microenvironments.
Free Research Field	生化学、細胞生物学、実験病理学
Academic Significance and Societal Importance of the Research Achievements	マウス口腔扁平上皮癌(OSCC)は、リンパ節転移能を獲得する悪性化に伴いMDSCを介する免疫抑制へと制御機能を変化させることを既に我々は示した。本研究では、発生初期のOSCCはMDSCを誘導せず、腫瘍微小環境において間葉系間質細胞を介した免疫抑制系を構築し、OSCCの放出するIL-1αがその機能を促進することを突き止めた。IL-1αがOSCC の新規免疫療法の標的分子となる可能性が示された。