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| Status |
Public on Apr 05, 2024 |
| Title |
Acidovorax temperans polarizes T17 cells and skews neutrophil maturation to promote lung adenocarcinoma development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Dysbiosis, or changes within the microbiome, is a common feature of solid tumors, however whether this dysbiosis directly contributes to tumor development is largely unknown. We previously characterized the human lung cancer microbiome and identified the Gram-negative Acidovorax temperans as enriched in tumors and associated with smoking status and TP53 mutations. To determine if A. temperans exposure could contribute to the development of lung cancer, we investigated its effect in a genetically engineered mouse model of lung adenocarcinoma driven by mutant Kras and Tp53. In comparison to control mice and those instilled with a commensal species Lactobacillus gasseri, we found that repeated A. temperans exposure accelerates tumor development and burden through infiltration of proinflammatory cells in the lungs. Comparing immune cell infiltrates at two timepoints revealed increased proinflammatory cells immediately following A. temperans instillation while later the number of T cells, especially IL-17+ cells, was increased. These data indicate a clear role for microbiota-induced inflammation as a key mechanism in the development of lung cancer, demonstrating that dysbiosis contributes to tumor growth.
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| Overall design |
Acidovorax teemperans, dysbiotic in human lungs, was repeatedly instilled into the lungs of mice bearing K-ras/p53 mtuations, to accelerate lung adenocarcinoma development. Lungs were harvested and RNA was extracted from tumors for sequencing.
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| Contributor(s) |
Stone J, Khan M, Harris C |
| Citation(s) |
38570533 |
| |
| Submission date |
Feb 27, 2024 |
| Last update date |
Apr 05, 2024 |
| Contact name |
Josh Stone |
| E-mail(s) |
josh.stone@nih.gov, harrisc@nih.gov, khanm@mail.nih.gov
|
| Phone |
240-760-7261
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| Organization name |
National Cancer Institue
|
| Department |
CCR
|
| Lab |
LHC
|
| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (45)
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| Relations |
| BioProject |
PRJNA1081431 |
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