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Prognostic Prediction and Therapeutic Application Focusing on the Oral Environment in Pancreatic Cancer Patients

Research Project

Project/Area Number 22K08694
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionKyushu University

Principal Investigator

SADAKARI Yoshihiko  九州大学, 医学研究院, 共同研究員 (80784503)

Co-Investigator(Kenkyū-buntansha) 森山 大樹  九州大学, 医学研究院, 共同研究員 (70586859)
田村 公二  九州大学, 大学病院, 助教 (90909582)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords膵癌 / 口腔内環境 / 歯周病原細菌 / 腫瘍微小環境 / 治療抵抗性 / 膵癌微小環境 / バイオマーカー
Outline of Research at the Start

膵癌は歯周病との関連を指摘されており、口腔内に複数種の特定の歯周病原細菌を保有している患者は膵癌発症リスクが高いことや、膵腫瘍内に特定の歯周病原細菌が検出された患者群は予後不良であることが報告されている。歯周病原細菌が膵発癌や予後に関連している報告から、今後、歯周病原細菌が膵癌治療の新たなターゲットとなる可能性がある。しかし、現時点で、歯周病原細菌が膵癌の進展に影響を与えるという報告は皆無である。本研究では、膵癌患者の口腔内環境、特に歯周病原細菌に着目した膵癌の進展に及ぼす影響を評価し、口腔機能管理の早期介入により膵癌の治療へ繋げることである。

Outline of Final Research Achievements

We demonstrated that one of the causative bacteria of periodontitis (XX) promotes the secretion of cytokines that induce immunosuppressive cells both in vitro and in vivo, contributing to tumor growth and a reduction in tumor-infiltrating T cells. Furthermore, we revealed that oral hygiene status correlates with the amount of intratumoral bacteria and resistance to chemotherapy. As part of the underlying mechanism, we confirmed in a mouse pancreatic cancer model that the periodontopathic bacterium XX alters the phenotype and function of a certain immune cell population, and that this bacterium increases resistance to chemotherapy.

Academic Significance and Societal Importance of the Research Achievements

これらの研究成果は、歯周病原細菌が何らかのかたちで腫瘍内にとどく可能性を示唆するものであり、また歯周病原細菌により免疫抑制性微小環境が構築されること、また治療への抵抗性を増強させることを示すものであり、新たな治療標的の発見や膵癌治療全体における口腔ケアの重要性を示唆する大きな成果であるといえる。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (6 results)

All 2024 2023

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Tumor-associated neutrophils upregulate Nectin2 expression, creating the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma2024

    • Author(s)
      Luo Haizhen、Ikenaga Naoki、Nakata Kohei、Higashijima Nobuhiro、Zhong Pingshan、Kubo Akihiro、Wu Chenyi、Tsutsumi Chikanori、Shimada Yuki、Hayashi Masataka、Oyama Koki、Date Satomi、Abe Toshiya、Ideno Noboru、Iwamoto Chika、Shindo Koji、Ohuchida Kenoki、Oda Yoshinao、Nakamura Masafumi
    • Journal Title

      Journal of Experimental & Clinical Cancer Research

      Volume: 43 Issue: 1 Pages: 258-258

    • DOI

      10.1186/s13046-024-03178-6

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1‐CXCR2 axis2023

    • Author(s)
      Hayashi Masataka、Ikenaga Naoki、Nakata Kohei、Luo Haizhen、Zhong PingShan、Date Satomi、Oyama Koki、Higashijima Nobuhiro、Kubo Akihiro、Iwamoto Chika、Torata Nobuhiro、Abe Toshiya、Yamada Yutaka、Ohuchida Kenoki、Oda Yoshinao、Nakamura Masafumi
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 9 Pages: 3666-3678

    • DOI

      10.1111/cas.15901

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Gram-Negative Bacteria Convert the Tumor Immune Microenvironment in Pancreatic Cancer after Preoperative Chemotherapy2024

    • Author(s)
      Akihiro Kubo, Chika Iwamoto, Kohei Nakata, Masataka Hayashi, Chikanori Tsutsumi,Yuki Shimada, Yutaka Yamada, Nobuhiro Higashijima, Takahito Matsuyoshi , Kento Hirotaka, Satomi Date, Koki Oyama, Toshiya Abe, Yusuke Watanabe, Noboru Ideno, Naoki Ikenaga, Kenoki Ohuchida, Yoshinao Oda, Masafumi Nakamura
    • Organizer
      55th American Pancreatic Association 2024 Annual Meeting
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 術前化学療法施行後の膵癌組織内グラム陰性菌が癌微小環境に与える影響の解明2024

    • Author(s)
      久保顕博、岩本千佳、仲田興平、小山虹輝、堤親範、島田有貴、山田裕、伊達聡美、東島亘宏、廣高健斗、松吉隆仁、阿部俊也、渡邉雄介、井手野昇、池永直樹、大内田研宙、小田義直、中村雅史
    • Organizer
      第55回日本膵臓学会大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] BIOLOGICAL EFFECTS OF INTRATUMOR PERIODONTAL PATHOGENS IN PANCREATIC CANCER2023

    • Author(s)
      Masataka Hayashi, Naoki Ikenaga, Kohei Nakata, Haizhen Luo, PingShan Zhong, Koki Oyama, Nobuhiro Higashijima, Akihiro Kubo, Satomi Date, Chika Iwamoto, Kenoki Ohuchida, Masafumi Nakamura
    • Organizer
      54th Annual American Pancreatic Association Meeting
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] INTRATUMOR FUSOBACTEIRUM NUCLEATUM PROMOTES THE PROGRESSION OF PANCREATIC CANCER VIA THE CXCL1/IL-8-CXCR2 AXIS2023

    • Author(s)
      Masataka Hayashi
    • Organizer
      Digestive Disease Week
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2026-01-16  

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