Targeting strategy against myeloid suppressor cells in mouse model of aged oral cancer

Research Project

Project/Area Number	16K11720
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Surgical dentistry
Research Institution	University of Toyama
Principal Investigator	Tomihara Kei 富山大学, 大学院医学薬学研究部(医学), 准教授 (70404738)
Co-Investigator(Kenkyū-buntansha)	山崎学新潟大学, 医歯学系, 助教 (10547516) 野口誠富山大学, 大学院医学薬学研究部(医学), 教授 (50208328)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	口腔癌 / 免疫抑制 / 免疫老化 / MDSC / PD-L1 / マウスモデル
Outline of Final Research Achievements	We showed that myeloid derived suppressor cells (MDSCs) are elevated in the peripheral blood, spleen, and tumor of mice with oral squamous cell carcinoma. In particular, MDSCs in tumors expressed PD-L1 more abundantly than those in other tissues. Accordingly, MDSCs from tumors, but not from the spleen, suppressed T cell proliferation in vitro. The results suggest that tumor-derived or immune factors result in the accumulation of phenotypically and functionally diverse populations of MDSCs in mice with oral squamous cell carcinoma. The proportion of MDSCs was significantly increased in aged oral cancer-bearing mice. The data also indicate that PD-L1 expression in MDSCs contributes to immune suppression, implying that targeting both myeloid-derived suppressor cells and PD-L1 would be an effective immunotherapeutic strategy against oral cancer.
Academic Significance and Societal Importance of the Research Achievements	本研究により、口腔扁平上皮癌における免疫老化を背景とした免疫抑制機序の一端を、MDSCの形質や機能の観点から解明することができれば、その標的化による新たな免疫療法の開発の一助と考えられる。また、MDSCの標的化分子の候補として免疫チェックポイント分子の発現が示唆されることから、免疫チェックポイント分子阻害薬に対する治療抵抗性の機序の解明と、その効果を最大限に引き出す新規治療法の開発に繋がることが期待される。