4.8 Article

A dysbiotic microbiome promotes head and neck squamous cell carcinoma

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ONCOGENE
卷 41, 期 9, 页码 1269-1280

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SPRINGERNATURE
DOI: 10.1038/s41388-021-02137-1

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资金

  1. NIH-NIDCR [R56 DE028959]
  2. NIH-NIAMS [R01 AR075033]
  3. Cancer League of Colorado
  4. Golfers Against Cancer
  5. University of Colorado Cancer Center
  6. University of Colorado GI and Liver Innate Immunity Program
  7. NIH-NIDCD [K23 DC014747]

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Recent studies have found dysbiotic oral microbiota and tumor-resident bacteria in patients with HNSCC, with elevated levels of Lactobacillus spp. and reduced levels of Neisseria spp. Furthermore, experimental evidence shows that depletion of microbiota delays oral tumorigenesis, while transfer of microbiota from mice with oral cancer accelerates tumorigenesis. These findings support the hypothesis that dysbiosis promotes HNSCC development.
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-naive 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.

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