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| Status |
Public on Jul 07, 2022 |
| Title |
Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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 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 an animal model of lung adenocarcinoma driven by mutant Kras and Tp53 alleles. This revealed A. temperans exposure accelerates tumor development and burden through infiltration of proinflammatory cells in the lungs. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling promoted maturation of the latter cell types which upregulated MHC II to activate CD4+ T cells. Activated T cells were then polarized to an IL-17A+ phenotype detectable in CD4+ and γδ populations. Furthermore, T17 cells shared a common gene expression profile predictive of poor survival in human LUAD cases. 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 |
CD45+ cells were sorted by FACS from tumor tissue within the mutant K-ras/p53 (KP) mouse model of lung adenocarcinoma and sent for scRNA-seq
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| Web link |
https://www.nature.com/articles/s41389-024-00513-6
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| Contributor(s) |
Stone JK, Khan M, Zhang C, von Muhlinen N, Harris CC |
| Citation(s) |
38570533 |
| |
| Submission date |
Jul 05, 2022 |
| Last update date |
Apr 05, 2024 |
| Contact name |
Joshua Stone |
| E-mail(s) |
josh.stone@nih.gov
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| Organization name |
NIH
|
| Street address |
37 Convent Drive Room 3050
|
| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA855893 |
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