Impact of oral anaerobic bacteria on the tumor immune microenvironment and prognosis of oral cancer

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BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for > 90% of oral cancers and has a poor prognosis. The microbiota affects the tumor microenvironment and tumor immune responses; however, the relationship between specific bacterial compositions and tumor-infiltrating immune cells in OSCC remains unclear. METHODS: The microbial diversity and compositions of tumor, normal mucosa, and stool samples from 42 OSCC patients were examined using 16S rDNA sequencing. Bacterial sampling was performed preoperatively by swabbing the tumor surface and normal mucosa and scraping a deep portion of the tumor. Differences in bacterial compositions between samples were examined using a linear discriminant analysis effect size analysis. To investigate the functional states of T cells, tumor-infiltrating immune cells were isolated and subjected to flow cytometry. The relationships among specific bacterial compositions, clinicopathological factors, and tumor-infiltrating immune cells were examined and the potential of microbiota-targeted therapy for OSCC was assessed. RESULTS: T cells (p = 0.01). Four bacterial genera, Parvimonas, Peptostreptococcus, Selenomonas, and Streptococcus were identified in comparisons of tumor surface samples between Groups A and B and between tumor surface and normal surface samples. A scoring system based on the ratio of anaerobic bacteria (Parvimonas, Peptostreptococcus, and Selenomonas) to aerobic bacteria (Streptococcus) correlated with impaired immune cell function (p = 0.02) and a poor prognosis (HR 9.61, 95% CI 1.15-80.63; p = 0.04). A simplified scoring system based on the Parvimonas to Streptococcus ratio showed a slightly poorer prognosis (HR 2.58, 95% CI 0.50-13.36; p = 0.26) and correlated with impaired immune cell function (p = 0.03). CONCLUSIONS: This is the first study to show a direct relationship between intratumoral anaerobic bacterial predominance and CD8⁺ T cell exhaustion in OSCC, suggesting a microbiota-dependent mechanism of immune dysfunction and disease progression. The bacteria scoring system has potential as a prognostic marker and guide for microbiota-targeted therapies to enhance anti-tumor immunity.