Development of innovative therapies for oral cancer metastasis targeting the formation of pre-metastasis niches by exosomes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10048
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Yoshuda Ryoji 熊本大学, 大学院生命科学研究部(医), 准教授 (10632458)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔扁平上皮癌 / エクソソーム / マイクロRNA / 腫瘍微小環境 / PDXモデル

Outline of Final Research Achievements

We conducted a study to develop an innovative treatment for oral cancer metastasis by targeting the formation of a pre-metastatic niche by exosomes. We found that PD-L1 is characteristically expressed in blood exosomes of patients with recurrent or metastatic oral cancer, and reported that it correlates with the therapeutic efficacy and prognosis of immunotherapy. We also performed multilayer omics analysis of exosomes extracted from patient sera, found miRNA-X associated with metastasis, and verified its clinical significance, which is now being submitted to an international journal. Furthermore, we established a highly metastatic subclone from a PDX cell line derived from an oral cancer patient and found multiple characteristic molecular expression profiles as a result of proteomic analysis. We are currently analyzing the biological significance of these molecules in the formation of the pre-metastatic niche.

Free Research Field

口腔がん

Academic Significance and Societal Importance of the Research Achievements

高転移性口腔癌による前転移ニッチ形成に着目して口腔がん転移の病態解明を目指した研究はほとんどなく、本研究成果は限界を迎えつつある口腔がんの転移診断や治療法開発に大きなパラダイムシフトをもたらし得ると考えられる。また、本研究の過程で、効率的にエクソソームを回収するキットの有用性や、口腔がんにおける体液診断の有用性についても証明することができた。以上の成果は、今後の研究を進める上での大きな成果であり、口腔がんの病態解明に寄与するだけでなく、他癌腫における高転移性腫瘍細胞の制御機構解明にも新たな知見をもたらし、その診断・治療法開発に大きく貢献すると考えられる。