Elucidation of the mechanism of the acquired chemotherapy resistance by tumor-associated macrophages in oral cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10070
• 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: Osaka University
• Principal Investigator: Morita Yoshihiro 大阪大学, 歯学部附属病院, 講師 (30590517)
• Co-Investigator(Kenkyū-buntansha): 鵜澤 成一 大阪大学, 大学院歯学研究科, 教授 (30345285)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔癌 / 化学療法耐性 / 腫瘍微小環境 / 腫瘍随伴Macrophage

Outline of Final Research Achievements

The concept of tumor microenvironment (TME) has been proposed and is currently being actively studied. The development of extracellular matrix in the TME, known as desmoplasia, is observed in many solid tumors. It is also strongly associated with poor prognosis and resistance to drug therapy. The aim of this study was to investigate desmoplasia-like changes in the TME before and after anticancer drug therapy in oral squamous cell carcinoma, and to evaluate the effect of anticancer drugs on the TME and the possible involvement of several inflammatory factors. Using a syngeneic oral cancer xenograft mouse model, we confirmed that anticancer drug administration caused desmoplasia-like changes in cancer tissues and showed that this was associated with inflammation.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

本研究では口腔癌の臨床検体や動物実験モデルを用いて腫瘍内への白血球の流入やTAMが引き起こす構造変化による化学療法耐性獲得のメカニズムを詳細に解明すると同時に、このメカニズムを臨床応用し、抗癌剤の治療効果の大幅な向上を目指すことを目的としており、抗癌剤による癌微小環境の変化を抑えることにより抗癌剤の効果を増強させようとする新しい治療戦略による薬物療法を確立しうる研究である。