Dynamics of immune regulation in oral chronic inflammation and cancer, and their connection to systemic immunity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H04066
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Azuma Miyuki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (90255654)
• Co-Investigator(Kenkyū-buntansha): 永井 重徳 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (50348801) ; 河野 洋平 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20401383) ; 大野 建州 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (80435635)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 免疫制御 / 口腔粘膜 / 口腔癌 / 免疫チェックポイント分子 / 制御細胞

Outline of Final Research Achievements

To clarify “negative immune responses” in the state of chronic clinical condition, we investigated regulatory cells in the chronic mucosal lesion and squamous cell carcinoma in the oral cavity. We observed two unique features of regulatory cells; Foxp3+ resident memory regulatory T cells in the buccal mucosa after repeated antigen painting, and IL-10-expressing CD206+ macrophages, which negatively regulate antigen-presenting capacity of nearby dendritic cells in the sublingual mucosa after repeated antigen painting. The studies using PD-1 immune checkpoint inhibitor-resistant squamous carcinoma cell models revealed that differences of myeloid cells in the tumor microenvironment (TME) affected the efficacies of additional immune therapy. Furthermore, our results demonstrated that immune profiles in the TME between tongue and skin inoculation were quite different.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

口腔粘膜慢性炎症における制御細胞および制御分子を標的とした慢性炎症制御の可能性が示された。本研究を発展させ、口腔癌におけるがん微少環境の免疫プロファイリングを明確にし、予後評価の指標となる免疫スコア（バイオマーカー）を同定すれば、口腔癌治療の指針に組み入れることができ、再発・転移症例に減少に繋がり、その社会的意義は大きい。また、免疫チェックポイント阻害剤で効果が得られない症例把握も可能となる。