Abstract 1283: Digital spatial profiling of metastatic brain tumors reveals association of the tumor microbiome with immune alterations in the tumor microenvironment

Abstract Introduction: Metastatic brain tumors are associated with significant morbidity and mortality. The microbiome has emerged as a novel hallmark of cancer, with a prominent role in tumor immunity and response to treatment. However, the role of the microbiome in brain tumors, and in particular brain metastasis, is largely unknown. We hypothesized that distinct microbial communities are associated with alterations in the tumor microenvironment in metastatic brain tumors. Methods: To evaluate the role of different microbial communities in brain metastasis, matched stool, saliva, and tumor samples were collected prospectively from patients with metastatic brain tumors who underwent surgical tumor resection at the University of Texas MD Anderson Cancer Center. Stool and saliva samples were sequenced via metagenomic shotgun sequencing and tumor samples were analyzed through 16S rRNA gene sequencing. The tumor microbiome was further characterized through confocal and electron microscopy and culture techniques. Lastly, we conducted digital spatial profiling using the NanoString GeoMx® platform to determine the spatial association of the tumor microbiome with tumor and immune transcriptome. Spatial single-cell transcriptome analysis of bacteria-positive and bacteria-negative cells within the tumor microenvironment is currently in progress using the CosMx® platform (NanoString Inc.). Results: Our computational and experimental analyses demonstrated that bacterial signals could be detected in metastatic brain tumors and exhibit an intracellular localization. Interestingly, we found that the tumor bacterial signatures in brain metastases were composed of commensal oral bacterial taxa but had limited overlap with the gut microbiome. Spatial transcriptome analysis demonstrated that tumor areas with high bacterial signal were associated with innate-immune mediated anti-bacterial responses, suggesting an active host response to intra-tumoral bacteria in metastatic brain tumors. Conclusion: Overall, this work demonstrates the presence of intracellular bacterial signal coupled with an anti-bacterial response within the tumor microenvironment of brain metastases. These findings offer a new perspective on the dynamic interaction between cancer, microbiome, and the brain microenvironment and can inform future mechanistic and translational studies to improve the outcome of brain tumor patients. Citation Format: Golnaz Morad, Ashish V. Damania, Brenda Melendez, Matthew C. Wong, Pranoti V. Sahasrabhojane, Sarah B. Johnson, Manoj Chelvanambi, Florentia Dimitriou, Jillian S. Losh, Nadim J. Ajami, Sherise D. Ferguson, Jennifer A. Wargo. Digital spatial profiling of metastatic brain tumors reveals association of the tumor microbiome with immune alterations in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1283.