Microbiome-derived extracellular vesicles regulate neutrophil differentiation into myeloid-derived suppressor cells in cancer microenvironments.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B110
Abstract ID: 5705

Presenting Author:
Lily Mussallem , Post-Baccalaureate Researcher at Univ. of Rochester Sch. of Med. & Dent.

Abstract:

Neutrophils are the most abundant type of white blood cells in the human body and serve as the first line of defense against invading pathogens. However, in response to the cancer microenvironment, neutrophils can transform into myeloid-derived suppressor cells (MDSCs), which exhibit immunosuppressive activity. The presence of MDSCs is often associated with negative prognosis and outcomes for cancer patients, but the mechanisms that trigger MDSC differentiation are not fully understood. The microbiome and its products have been linked to cancer progression, often due to gut dysbiosis caused by cancer treatments. However, there is a gap in research regarding the role of the microbiome in a steady state. We hypothesize that microbiome-derived extracellular vesicles that cross the gut barrier into circulation can influence neutrophil heterogeneity and lead to distinct differentiation of neutrophils into MDSCs in cancer microenvironments. To test this, we used ex vivo mouse models of microbiome training. We found that naïve bone marrow neutrophils from microbiome-free mice and microbiome-induced mice did not exhibit heterogeneous responses to the cancer microenvironment, as expected. However, in circulating neutrophils, we observed higher levels of activation and arginase production in microbiome-trained mice in response to cancer microenvironments. Overall, this suggests that the microbiome may play a role in neutrophil differentiation into MDSCs.