838 The role of microbiota in metastatic brain tumors

作者：Sarah B. Johnson, Golnaz Morad, Nadim J. Ajami, Jennifer A. Wargo, Matthew Wong, Matthew Lastrapes · 发表于：Regular and Young Investigator Award Abstracts · 年份：2021 · DOI：10.1136/jitc-2021-sitc2021.838 · 被引用次数：2 · 研究领域：Gut microbiota and health、Cancer Immunotherapy and Biomarkers、Epigenetics and DNA Methylation

Background Despite the substantial advances in the treatment of systemic cancer, brain metastases are still responsible for significant morbidity and mortality, necessitating a better understanding of the mechanisms underlying this disease. Microbiota has emerged as a significant hallmark of cancer. Our group and others have demonstrated a prominent role for gut and intratumoral microbiota in tumorigenesis, tumor immunity, and response to treatment. However, the role of microbiota in brain metastasis is poorly understood. We hypothesize that distinct microbial communities can alter the immune microenvironment in the brain and modulate the different steps of brain metastasis formation. Methods To explore the role of microbiota in brain metastasis, we evaluated the gut and oral microbial signatures in brain metastasis patients through shotgun metagenomics sequencing. Furthermore, we conducted mechanistic in vivo studies in which the gut microbiota was depleted in conventionally raised mice using a broad-spectrum non-absorbable antibiotic regimen. Subsequently, melanoma tumor cells were injected intracranially to evaluate the effect of gut microbiota depletion and associated immune changes on tumor growth. Tumor growth was measured through in vivo bioluminescent imaging and histology. Peripheral and tumor immune profiling was conducted through flow cytometry and immunohistochemistry. Results Our clinical studies demonstrated the enrichment of distinct bacterial and viral ta...