Basic study for the development of immunotherapy based on the microenvironment of oral cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03140
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kochi University
• Principal Investigator: Yamamoto Tetsuya 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00200824)
• Co-Investigator(Kenkyū-buntansha): 笹部 衣里 高知大学, 教育研究部医療学系臨床医学部門, 講師 (40363288) ; 北村 直也 高知大学, 教育研究部医療学系臨床医学部門, 講師 (70351921) ; 仙頭 慎哉 高知大学, 教育研究部医療学系臨床医学部門, 助教 (30635264)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 口腔扁平上皮癌

Outline of Final Research Achievements

In head and neck cancer, the efficacy of cancer immunotherapy using immune checkpoint inhibitors (ICIs) is limited, and elucidation of the resistance mechanism is an urgent task to improve its efficacy. In this study, we investigated the intrinsic effects of PD-L1 expressed in oral squamous cell carcinoma (OSCC) cells and its mechanism. Furthermore, we examined the influences of cytotoxic drugs and EGFR-targeting drugs including erlotinib and cetuximab on PD-L1 expression in OSCC cells. We also analyzed the dynamic changes in PD-L1 expression during a series of treatments using clinical specimens from oral cancer patients with recurrent or distant metastasis treated with nivolumab and clarified the relationship with the therapeutic effect of ICI therapy.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

ICI療法により生存期間の若干の延長は認められるものの、奏効率の低さ、治療効果の個体差、治療薬が高額であること、免疫関連有害事象など解決すべき数多くの問題がある。本研究では、癌細胞に発現するPD-L1そのものを標的とする新規治療法、ICI療法と殺細胞薬、分子標的薬の併用、また口腔癌の一連の治療過程においてどのタイミングでICI療法を行うのが効果的なのかを提案するものである。