A dysbiotic microbiome promotes head and neck squamous cell carcinoma

• Published in: Oncogene Vol. 41; no. 9; pp. 1269 - 1280
• Main Authors: Frank, Daniel N., Qiu, Yue, Cao, Yu, Zhang, Shuguang, Lu, Ling, Kofonow, Jennifer M., Robertson, Charles E., Liu, Yanqiu, Wang, Haibo, Levens, Cassandra L., Kuhn, Kristine A., Song, John, Ramakrishnan, Vijay R., Lu, Shi-Long
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.02.2022; Nature Publishing Group
• Subjects: 38/23; 38/77; 4-Nitroquinoline 1-oxide; 4-Nitroquinoline-1-oxide - toxicity; 631/326; 64/60; 692/53/2421; Animals; Antibiotics; Apoptosis; Carcinogenesis; Cell Biology; Disease Models, Animal; Dysbacteriosis; Dysbiosis - microbiology; Female; Germfree; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - microbiology; Head and Neck Neoplasms - pathology; Human Genetics; Humans; Internal Medicine; Lactobacillus; Male; Medicine; Medicine & Public Health; Mice; Microbiomes; Microbiota; Microorganisms; Oncology; Oral cancer; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - microbiology; Squamous Cell Carcinoma of Head and Neck - pathology; Tumorigenesis
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-021-02137-1

Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp . and Neisseria spp . are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp . was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.