The research of regulatory T cell depletion therapy for tongue cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kumamoto University
• Principal Investigator: Orita Yorihisa 熊本大学, 大学院生命科学研究部(医), 教授 (90362970)
• Co-Investigator(Kenkyū-buntansha): 三木 健太郎 岡山大学, 大学病院, 助教 (20747448) ; 佐藤 康晴 岡山大学, 保健学研究科, 教授 (00579831)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: HNSCC / 4NQO / Treg / DEREGマウス

Outline of Final Research Achievements

A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue squamous cell carcinoma (SCC) was established. We found that the amount of Tregs of the experimental mice at the tumor site was over 10 times as much as control mice at the early stage of tumor progression. This time 4NQO was administered to DEREG (Depletion of regulatory T cell) mice same as the former experiments using wild-type-mice to develop tongue SCC, and diphtheria toxin was given to exclude Treg at the early stage of tumor progression. We found that further progression of the tongue SCC was blocked and the mice were free from SCC. However, it was difficult to breed DEREG mice to the number enough for statistical analysis, and moreover, some of them did not develop tongue SCC even without diphtheria toxin. We are still studying about the reasons for dispersion of the results.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

制御性T細胞 (Treg)の浸潤は近年多くの癌種において予後不良因子として報告されており、例えば分子標的治療薬イピリムマブはTregの機能低下および腫瘍組織におけるTreg数の減少により腫瘍免疫反応を亢進させ抗腫瘍効果を狙ったものです。この治療薬を癌進行のどの時期に投薬するのが有効かわかれば、より患者の肉体的・経済的負担に見合ったカスタマイズされた治療計画の立案が可能になると思われます。また、この動物実験で観察されたように前癌病変の段階でTregを制御することによってそれ以上の進行を食い止められるのであれば、癌予防治療にもつながると考えています。