Elucidating the mechanisms underlying the ability of pathogenic Acidovorax temperans and its derived outer membrane vesicles to promote lung cancer progression

The lung is colonized by a wide range of microbes, and alterations in the microbial composition may contribute to the carcinogenesis process. We previously characterized a distinct group of taxa and found higher amounts of the Gram-negative microbe Acidovorax temperans (A. temperans) in the cancerous human lung tissue. Our collaborators highlight that enrichment of A. temperans in the lung microbial community modulates the immune microenvironment and therefore contributes to tumor development. Gram-negative bacteria naturally release outer membrane vesicles (OMVs). OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules directly into the host cells. we hypothesize that the interactions of A. temperans with host lung cancer cells, leading to accelerated inflammation-based tumorigenesis, are facilitated through OMVs shed by the bacteria. Our preliminary results suggest that A. temperans OMVs are taken up by A549 lung cancer cells and that A. temperans OMVs are strong pro-inflammatory stimulators in differentiated THP-1 cells. In addition, macrophages exposed to A. temperans OMVs overexpress SIRPα which is associated with tumor cell immune escape and tumor progression. Notably, we also optimized in vivo protocol in which we were able to introduce A. temperans OMVs into the lungs of mice by intranasal administration. Intranasal administration of A. temperans OMVs leads to increased secretion of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, TNFα, and GM-CSF mRNA levels in the lung tissue. Taken together, our preliminary findings suggest that the interactions between OMVs shed by A. temperans and lung cancer microenvironment lead to accelerated, inflammation-based tumorigenesis.