BSBM-09 THE ROLE OF ORAL MICROBIOTA IN THE DEVELOPMENT OF METASTATIC BRAIN TUMORS.

Abstract Brain metastases (BrMs) often present as a late intracranial manifestation of systemic cancer, following multiple courses of systemic cancer treatments (e.g., chemotherapy, radiotherapy, immunotherapy). Oral complications are common side effects of systemic cancer treatments, often resulting in disruption or dysbiosis of the oral microbiota (OMD). OMD has been implicated in the context of systemic diseases such as cardiovascular, metabolic, and neurodegenerative diseases. However, the potential impact of OMD in cancer progression, specifically BrM development, has been largely understudied. In this study, we investigated the impact of OMD in the development of melanoma BrM. Subcutaneous melanoma-bearing mice (B16-F10 or BP) without intracranial lesions were used to model the pre-metastatic niche stage. To induce OMD, mice received anti-septic mouthwashes every 12 h for a total of 10 days, which led to a significant decrease in alpha diversity and alteration of the oral microbiota composition. The gut microbiota remained unchanged during this study. OMD was associated with a significant increase in subcutaneous melanoma tumor growth. Proteomic profiling of brain tissue via mass spectrometry demonstrated an enrichment of acute inflammatory proteins and a decrease in peri-vascular extracellular matrix molecules in OMD mice, suggestive of peri-vascular remodeling. In contrast, evaluation of the brain immune microenvironment via immunohistochemistry and spatial profiling demonstrated minimal immune alterations. Preliminary studies combining this model with intracranial injection of tumor cells suggested an increase in the incidence of BrM development associated with OMD. Together, our findings demonstrate that OMD can modulate the brain environment, specifically the peri-vascular area, and may contribute to melanoma BrM biology. These studies lay the foundation for ongoing research in our group to delineate the contribution of systemic treatment-induced OMD in BrM development and to leverage this knowledge to improve the outcome of this disease via microbiome-linked accessible and cost-effective strategies.