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Elucidation of the mechanism of resistance to immune checkpoint inhibitors in oral squamous cell carcinoma and novel therapeutic strategies

Research Project

Project/Area Number 21K10142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionKumamoto University

Principal Investigator

Nagata Masashi  熊本大学, 病院, 医員 (10635791)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords口腔扁平上皮癌 / 免疫チェックポイント阻害剤 / 治療マーカー / 免疫チェックポイント阻害薬 / 感受性マーカー / 口腔癌 / 細胞外小胞 / OSCC / ICIs / 治療抵抗性
Outline of Research at the Start

口腔癌におけるICIs耐性機序の解明および新たな治療戦略の開発を目的として、実際に免疫チェックポイント阻害薬を投与した患者検体やPatient Derived Xenograft: PDXモデルを使用し、新たな分子機構の解明行う。

Outline of Final Research Achievements

As the efficacy of immune checkpoint inhibitors (ICIs) in oral squamous cell carcinoma has been attracting attention, we explored the possibility of PDL1, a marker of ICIs, as a treatment prognostic factor. The PD-L1EVs-high group had a worse prognosis in PFS, PFS2, and OS compared to the PD-L1EVs-low group, and PD-L1EVs was an independent prognostic factor for OS. Next, we analyzed the relationship between nutritional indicators and T cell exhaustion in peripheral blood, and found that patients with low OPNI values had more advanced T cell exhaustion of CTLs in peripheral blood, suggesting that poor nutritional status may affect the immune status of the whole body.

Academic Significance and Societal Importance of the Research Achievements

治療予後因子の解明により、患者1人1人に適した抗腫瘍薬を選択することが可能になり、治療効果向上が期待される。また、根治的加療が不可能である進行例においても、効果的な薬剤の使用や、補助療法の併用にてQOLの維持に繋がると思われる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (1 results)

All 2023

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Programmed death-ligand 1-expressing extracellular vesicles are a prognostic factor in patients with oral squamous cell carcinoma treated with immune checkpoint inhibitors2023

    • Author(s)
      Seki Yuki、Yamana Keisuke、Yoshida Ryoji、Inoue Junki、Shinohara Kosuke、Oyama Toru、Kubo Ryuta、Nagata Masashi、Kawahara Kenta、Hirayama Masatoshi、Takahashi Nozomu、Nakamoto Masafumi、Hirosue Akiyuki、Kariya Ryusho、Okada Seiji、Nakayama Hideki
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: in press Issue: 4 Pages: 518-525

    • DOI

      10.1016/j.ajoms.2023.12.007

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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