Effect of oral health on efficacy of immune checkpoint inhibitors

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K19332
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57080:Social dentistry-related
• Research Institution: Nara Medical University
• Principal Investigator: Nakashima Chie 奈良県立医科大学, 医学部, 研究員 (40812657)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 細菌叢 / ウェルシュ菌 / クローディン4 / YAP / 上皮間葉移行 / がん幹細胞性

Outline of Final Research Achievements

Although C. perfringens impair tight junctions, in oral squamous cell carcinoma, intratumoral C. perfringens induced YAP activation through intracellular translocation of claudin-4, resulting in enhanced EMT and stemness. Similarly, C. perfringens was found to contribute to the malignant transformation of colon cancer precancerous lesions SSA/P-D. Furthermore, in renal cell carcinoma, EphA2-PKCε resulted in the activation of YAP by intracellular translocation of claudin-4, similar to C. perfringens. Thus, the non-tight junction claudin-4-YAP pathway may represent a novel target for cancer therapy.

Free Research Field

口腔衛生学

Academic Significance and Societal Importance of the Research Achievements

体内細菌叢の細菌と癌との関係は未だ不明な点が多い。この腫瘍－細菌連関の免疫や発癌への影響をタイトジャンクションという切り口から解明することにより、新たな癌の悪性化機序を見出し、新規治療標的を抽出することを本研究の目的とする。本研究の結果は、腫瘍－細菌連関を標的とする口腔衛生、プロバイオティックスや分子標的治療の開発に有用な知見をもたらすことが期待される。