Dynamics of immune regulation in oral chronic inflammation and cancer, and their connection to systemic immunity
| Project/Area Number |
18H04066
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2019: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2018: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
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| 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 / 慢性炎症 / 免疫抑制御 / T細胞 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] VISTA expressed in tumour cells regulates T cell function2018
Author(s)
Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
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Journal Title
British Journal of Cancer
Volume: 120
Issue: 1
Pages: 115-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Silencing of PD-L2/B7-DC by topical application of small iInterfering RNA inhibits elicitation of contact hypersensitivity.2019
Author(s)
Furusawa E, Ohno T, Nagai S, Noda T, Komiyama T, Kobayashi K, Hamamoto H, Miyashin M, Yokozeki H, Azuma M.
Organizer
AAI 2019 (The American Association of Immunologists, Immunology2019)
Related Report
Int'l Joint Research
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[Presentation] Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy2018
Author(s)
Nishii N, Tachinami H, Kondo Y, Xia Y, Kashima Y, Ohno T, Nagai S, Li L, Lau W, Harada H, Azuma M
Organizer
15th International Symposium on Dendritic Cells
Related Report
Int'l Joint Research
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