Work

Intratumoral Capnocytophaga leadbetteri promotes cancer cells proliferation and recruits neutrophils by activating TLR4/MyD88/NF-κB axis in oral squamous cell carcinoma

Year: 2026

Type: article

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.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-015159