A dysbiotic microbiome promotes head and neck squamous cell carcinoma.
Daniel N FrankYue QiuYu CaoShuguang ZhangLing LuJennifer M KofonowCharles E RobertsonYanqiu LiuHaibo WangCassandra L LevensKristine A KuhnJohn SongVijay R RamakrishnanShi-Long LuPublished in: Oncogene (2022)
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.
Keyphrases
- endothelial cells
- mouse model
- pluripotent stem cells
- end stage renal disease
- high glucose
- ejection fraction
- type diabetes
- microbial community
- chronic kidney disease
- metabolic syndrome
- dna methylation
- genome wide
- prognostic factors
- patient safety
- adipose tissue
- oxidative stress
- peritoneal dialysis
- binding protein
- skeletal muscle
- adverse drug