The development of novel prevention and histological diagnosis methods for oral squamous cell carcinoma focusing on M1 macrophages

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19157
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kobe University
• Principal Investigator: Shigeoka Manabu 神戸大学, 医学研究科, 助教 (20778716)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 口腔扁平上皮癌 / マクロファージ / 舌癌 / 舌白板症 / CD163 / IL-10 / CCL20 / 発癌

Outline of Final Research Achievements

Oral squamous cell carcinoma (OSCC) is an intractable cancer, and its prevention, early diagnosis, and early treatment are important. Therefore, the elucidation of oral carcinogenic mechanism is urgent. In this study, it was clarified that M2 marker CD163-positive macrophages accumulated beneath the basement membrane serve as a biological promoter via tumor immunosuppression in the progression of oral squamous intraepithelial neoplasia and that they accumulated not only to the cancer nest but also to its surrounding epithelium, depending on the presence of stromal invasion. In addition, we found that OSCC cell-derived CCL20, which is M1 macrophage-related chemokine, induced by interaction with intraepithelial macrophages enhance the CD163 expression of macrophages and enhance malignant phenotype of OSCC cells.

Free Research Field

口腔腫瘍学

Academic Significance and Societal Importance of the Research Achievements

口腔扁平上皮の発癌過程は未だ解明されていない点が多く、さらには、これまでマクロファージに着眼した検討は少数であった。本研究の学術的・社会的意義は、口腔の発癌段階におけるマクロファージはM1/M2理論のみでは答えの出せない多様な活性を示すことを見出し、マクロファージの分布や癌細胞との位置関係の変化、それに伴い微小環境中に誘導されるCCL20が口腔癌の予防や早期病変に対する診断の標的となる可能性を示したことである。
これらの成果は、癌進展への関与が注目される癌細胞-マクロファージ相互作用を基軸とした口腔扁平上皮「発癌」の新たな制御法開発への足がかりを提供するものと期待される。