Acidovorax temperans polarizes T17 cells and skews neutrophil maturation to promote lung adenocarcinoma development

Stone, J. K.; von Muhlinen, N.; Zhang, C.; Robles, A. I.; Vega-Valle, E.; Miyanaga, A.; Matsumoto, M.; Greathouse, K. L.; Cooks, T.; Trinchieri, G.; Harris, C. C.

doi:10.1101/2022.12.20.521215

bioRxiv · 10.1101/2022.12.20.521215

Acidovorax temperans polarizes T17 cells and skews neutrophil maturation to promote lung adenocarcinoma development

Stone, J. K.·von Muhlinen, N.·Zhang, C.·Robles, A. I.·Vega-Valle, E.·Miyanaga, A.·Matsumoto, M.·Greathouse, K. L.·Cooks, T.·Trinchieri, G.·Harris, C. C.

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Abstract

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 Acidovorax temperans as enriched in tumors. In this study, we instilled A. temperans in an animal model driven by mutant Kras and Tp53 alleles. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic genotype with increased cytokine signaling, with a global shift away from IL-1{beta} signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells which polarized to an IL-17A+ phenotype detectable in CD4+ and {gamma}{delta} populations. T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate dysbiosis promotes tumor growth by modulating inflammation.

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Stone, J. K., von Muhlinen, N., Zhang, C., Robles, A. I., Vega-Valle, E., Miyanaga, A., Matsumoto, M., Greathouse, K. L., Cooks, T., Trinchieri, G., Harris, C. C.. 2022-12-20. Acidovorax temperans polarizes T17 cells and skews neutrophil maturation to promote lung adenocarcinoma development. https://doi.org/10.1101/2022.12.20.521215

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