Intra-tumoral bacterial signals are associated with distinct immune niches in metastatic brain tumors 3692

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Abstract Description Metastatic brain tumors (BrM) are associated with significant morbidity and mortality. Despite significant advances in understanding the role of microbiome in cancer and tumor immunity, the impact of microbiome in BrM remains largely unknown. In this study, we used a prospectively collected cohort of BrM tumors to explore the spatial distribution of microbial elements in BrM and determine their correlation with the tumor microenvironment. We employed pan-bacterial 16S fluorescent in situ hybridization and Small Molecular Imaging (SMI, CosMx® Platform, NanoString) and demonstrated that bacterial signals can be detected in BrM tumors, are intracellular and distributed across tumor and immune cells. We investigated the spatial association of these bacterial signals with specific niches in the tumor microenvironment using SMI and Digital Spatial Profiling (DSP, GeoMx® Platform, NanoString). We demonstrated that tumor regions with high bacterial signals were associated with in anti-bacterial signatures indicative of TLR pathway activation, enrichment of neutrophils and neutrophil enzymes, as well as distinct metabolic signatures. Collectively, our studies introduce intracellular bacterial signal as a novel component of the brain tumor microenvironment and demonstrate its correlation with distinct immune signatures. These findings can guide future mechanistic and translational studies to elucidate the functional role of the intra-tumoral bacterial signal in brain tumor biology. Funding Sources This study was supported by the National Cancer Institute (F32CA260769), the Andrew M. McDougall Brain Metastasis Research Award, and the Dr. Marnie Rose Foundation. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

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