{
  "abstract": "Background Intratumoral bacteria influence the progression and treatment response of solid tumors through multiple mechanisms. Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck; however, the role of intratumoral bacteria in OSCC initiation and progression remains poorly understood.Methods We integrated 21 public 16S rRNA gene amplicon sequencing (16S rRNA-seq) datasets (comprising 954 normal and 1,627 OSCC samples) to profile oral microbiota dysbiosis across 4 sample types (saliva, oral rinse, swab, and tissue). Subsequent analysis via five-region 16S rRNA-seq and fluorescence in situ hybridization revealed a specific species enriched in OSCC tissues. The functional role of this bacterium and its underlying mechanism were then elucidated using in vitro and in vivo models, including germ-free mice.Results Our analysis revealed a reduced diversity of the oral microbiota in patients with OSCC, along with a significant enrichment of the Capnocytophaga in swab and tissue samples. Capnocytophaga leadbetteri (C. leadbetteri), a species within Capnocytophaga, was further confirmed to be specifically enriched in OSCC tissues. Functional studies demonstrated that C. leadbetteri alone is sufficient to induce epithelial hyperproliferation and a protumorigenic inflammatory niche, and it promotes established OSCC progression. Mechanistically, C. leadbetteri activates the TLR4/MyD88/NF-κB pathway in OSCC cells, stimulating tumor cell proliferation and the expression of chemokines (Cxcl1, Cxcl2, Ccl5, and Ccl7). This leads to the recruitment of tumor-associated neutrophils and establishes a protumorigenic microenvironment.Conclusions Our findings establish a protumorigenic role for intratumoral C. leadbetteri in OSCC and highlight its potential as a novel diagnostic and therapeutic target.",
  "authors": [
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yunmei Dong"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Kuichi Chen"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Hongya Zheng"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Wei Liu"
    },
    {
      "affiliations": [
        "College of Medical Informatics, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Li Yan"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Zhuoyan Luo"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yuqi Qin"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Shiping Lv"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Bing Yang"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Fangchun Chen"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yiyun Liu"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Juncai Pu"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Peng Xie"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Ping Ji"
    },
    {
      "affiliations": [
        "The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Xin Jin"
    }
  ],
  "title": "Intratumoral Capnocytophaga leadbetteri promotes cancer cells proliferation and recruits neutrophils by activating TLR4/MyD88/NF-κB axis in oral squamous cell carcinoma",
  "uid": "61594b64-9cad-5070-827d-b1eb713c8c30"
}