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Identification for dysbiosis in oral bacterial flora of patients with oral squamous cell carcinoma and development of innovative combination oncoimmune therapy

Research Project

Project/Area Number 20K10130
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 InstitutionNagasaki University

Principal Investigator

Okano Shinji  長崎大学, 医歯薬学総合研究科(医学系), 教授 (10380429)

Co-Investigator(Kenkyū-buntansha) 田中 芳彦  福岡歯科大学, 口腔歯学部, 教授 (00398083)
池邉 哲郎  福岡歯科大学, 口腔歯学部, 教授 (20202913)
坂上 竜資  福岡歯科大学, 口腔歯学部, 教授 (50215612)
平木 昭光  福岡歯科大学, 口腔歯学部, 教授 (60404034)
橋本 憲一郎  福岡歯科大学, 口腔歯学部, 准教授 (00412619)
吉永 泰周  福岡歯科大学, 口腔歯学部, 准教授 (60452869)
吉住 潤子  福岡歯科大学, 口腔歯学部, 講師 (40596376)
池田 哲夫  福岡歯科大学, 口腔歯学部, 客員教授 (60585701)
前原 喜彦  福岡歯科大学, 口腔歯学部, 客員教授 (80165662)
Project Period (FY) 2020-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords口腔扁平上皮 / 口腔内細菌叢 / メタゲノム解析 / Dysbiosis / 癌複合免疫療法 / 口腔扁平上皮癌
Outline of Research at the Start

口腔内細菌叢は約700種の菌種で構成され、デンタルプラークの細菌密度は糞便の同等あるいはそれ以上である。粘膜免疫は口腔・腸内細菌叢と量的・質的にバランスを保っており、dysbiosisと呼ばれる細菌叢の恒常性の変容は免疫異常を発生させると考えられている。本研究では、口腔扁平上皮癌患者に特徴的な口腔内細菌叢のプロフィールを解析し、そのデーターに基づいた動物実験により、口腔内細菌叢の口腔癌発癌・進展と口腔粘膜免疫及び腫瘍免疫応答へ及ぼす影響を明らかにし、その分子機序を標的とする口腔扁平上皮癌の予防並びに癌免疫複合療法を増幅させる革新的がん治療薬開発の契機を得る。

Outline of Final Research Achievements

In this study, in head and neck cancer, at the genus level, Prevotella, Pseudomonas, Firmicutes, Fusobacterium, and Proteobacteria were dominant, while at the family level, Prevotella, Pseudomonas, Streptococcus, Fusobacterium, and Bacillus were dominant at the genus level. The increase in Proteobacteria, Bacteroidetes, and Pseudomonas was associated with an increase in the intestinal microbiota, and the Actinobacteria phylum and Prevotella genus were considered worthy of further study as bacteria that may influence the efficacy of immune checkpoint inhibitors.

Academic Significance and Societal Importance of the Research Achievements

本研究により、頭頸部および食道扁平上皮癌患者において特徴的な口腔内細菌叢の変化が同定され、特にPrevotella属とPseudomonas属が癌の進展、予後、および免疫応答に重要な役割を果たす可能性が示唆された。これらの知見は、口腔内細菌叢を介した個別化がん治療の実現に向けた重要な一歩であり、国際的にも高く評価される内容と考えられる。今後、これらの細菌を標的とした新たな診断・治療戦略の開発が期待され、特に免疫チェックポイント阻害剤の効果予測および治療効果向上のためのバイオマーカーとしての臨床応用が注目される。

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (12 results)

All 2024 2023 2022 2021 2020 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Remarks (1 results)

  • [Journal Article] 咽頭後間隙原発滑膜肉腫の1例2024

    • Author(s)
      前田 耕太郎, 大野 純希, 岡野 慎士, 西 秀昭, 熊井 良彦
    • Journal Title

      耳鼻と臨床

      Volume: 70 Pages: 84-89

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Prospective Observational Study Analyzing the Diversity and Specific Composition of the Oral and Gut Microbiota in Lung Cancer Patients2024

    • Author(s)
      SHOJI FUMIHIRO、MINEMURA AYAKA、KOZUMA YUKA、NOUNO TAKASHI、TAKEOKA HIROAKI、MATSUMOTO ASAMI、OKAMOTO MASAKI、YAMAGUCHI MASAFUMI、YAMAZAKI KOJI、MAEHARA YOSHIHIKO
    • Journal Title

      Anticancer Research

      Volume: 44 Issue: 11 Pages: 5067-5080

    • DOI

      10.21873/anticanres.17331

    • Related Report
      2024 Annual Research Report
  • [Journal Article] DKK3 expression is correlated with poorer prognosis in head and neck squamous cell carcinoma: A bioinformatics study based on the TCGA database2023

    • Author(s)
      Katase Naoki、Nishimatsu Shin-ichiro、Yamauchi Akira、Okano Shinji、Fujita Shuichi
    • Journal Title

      Journal of Oral Biosciences

      Volume: 65 Issue: 4 Pages: 334-346

    • DOI

      10.1016/j.job.2023.09.002

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathologic complete response after chemotherapy with atezolizumab plus bevacizumab for hepatocellular carcinoma with tumor thrombus in the main portal trunk2023

    • Author(s)
      Kurisaki Ken、Soyama Akihiko、Hara Takanobu、Matsushima Hajime、Imamura Hajime、Tanaka Takayuki、Adachi Tomohiko、Ito Shinichiro、Kanetaka Kengo、Hidaka Masaaki、Okano Shinji、Eguchi Susumu
    • Journal Title

      Digestive Surgery

      Volume: - Issue: 1-2 Pages: 84-89

    • DOI

      10.1159/000529405

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Outcome of Conversion Liver Resection Surgery by Lenvatinib Treatment: A Single Center Experience2022

    • Author(s)
      HIDAKA MASAAKI、HARA TAKANOBU、SOYAMA AKIHIKO、SASAKI RYU、MATSUSHIMA HAJIME、TANAKA TAKAYUKI、HAMADA TAKASHI、IMAMURA HAJIME、ADACHI TOMOHIKO、KANETAKA KENGO、MIYAAKI HISAMITSU、OKANO SHINJI、EGUCHI SUSUMU
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 6 Pages: 3049-3054

    • DOI

      10.21873/anticanres.15791

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three‐dimensional imaging of intramural perineural invasion in colorectal cancer: Three‐dimensional reconstruction approach with multiple immunohistochemically stained sections2022

    • Author(s)
      Miyashita Yu、Ikeda Tetsuo、Shinto Eiji、Okano Shinji、Korehisa Shotaro、Shimazaki Hideyuki、Oki Eiji、Ueno Hideki、Oda Yoshinao、Mori Masaki
    • Journal Title

      Pathology International

      Volume: . Issue: 5 Pages: 293-299

    • DOI

      10.1111/pin.13222

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.2022

    • Author(s)
      Tominaga T, Nonaka T, Fukuda A, Moriyama M, Oyama S, Ishii M, Sawai T, Okano S, Nagayasu T.
    • Journal Title

      Clin J Gastroenterol.

      Volume: 15 Issue: 1 Pages: 134-139

    • DOI

      10.1007/s12328-021-01543-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histomorphological investigation of intrahepatic connective tissue for surgical anatomy based on modern computer imaging analysis.2021

    • Author(s)
      Ikeda T, Okano S, Hashimoto N, Kimura K, Kudo K, Tsutsumi R, Sasaki S, Kawasaki J, Miyashita Y, Wada H.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: 28 Issue: 1 Pages: 76-85

    • DOI

      10.1002/jhbp.753

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.2020

    • Author(s)
      Ikeda T, Aida M, Yoshida Y, Matsumoto S, Tanaka M, Nakayama J, Nagao Y, Nakata R, Oki E, Akahoshi T, Okano S, Nomura M, Hashizume M, Maehara Y.
    • Journal Title

      Br J Surg.

      Volume: 107 Issue: 12 Pages: 1673-1685

    • DOI

      10.1002/bjs.11654

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] LINE-1 Hypomethylation Is Associated With Malignant Traits and Cell Proliferation in Lung Adenocarcinoma.2020

    • Author(s)
      Kitahara H, Okamoto T, Shimamatsu S, Kohno M, Morodomi Y, Tagawa T, Kitao H, Okano S, Oda Y, Maehara Y, Mori M.
    • Journal Title

      Anticancer Res.

      Volume: 40 Issue: 10 Pages: 5659-5666

    • DOI

      10.21873/anticanres.14579

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cisplatin-induced programed cell death ligand-2 expression is associated with metastasis ability in oral squamous cell carcinoma2020

    • Author(s)
      Sudo S, Kajiya H, Okano S, Sasaki M, Katsumata Y, Ohno J, Ikebe T, Hiraki A, Okabe K
    • Journal Title

      Cancer Sci

      Volume: 111 Issue: 4 Pages: 1113-1123

    • DOI

      10.1111/cas.14336

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks]

    • URL

      https://nagasaki-u-pathology.com/summary/

    • Related Report
      2024 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2026-01-16  

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