Abstract P018: Gut microbiota-driven alterations in tumor immunity can modulate the growth of metastatic brain tumors

Abstract

Abstract Background: Metastatic brain tumors are associated with significant morbidity and mortality. The current limited understanding of the mechanisms underlying brain metastasis has hindered the development of efficient diagnostics and therapeutics for this disease. Microbiota has emerged as a novel hallmark of cancer, with a prominent role in tumorigenesis, tumor immunity, and response to treatment. However, the role of the microbiota in tumor metastasis, and in particular 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 gut microbiota in brain metastasis, we depleted gut microbiota 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: Depletion of the gut microbiota in mice decreased tumor growth in the brain. Evaluation of the peripheral and tumor immune profiles suggested the underlying mechanisms to involve alterations in the circulating cytokine profiles and an increase in anti-tumor T cell activity. Conclusion: Our clinical studies suggest the association of distinct microbial communities with brain metastasis. Our pre-clinical findings demonstrate that the absence of gut microbiota can modulate the regulation of T cell activity to induce an anti-tumor response in the brain. Further studies, currently in progress, will determine the mechanistic role of dysbiotic microbiota and distinct microbial communities in this process. Citation Format: Golnaz Morad, Sarah B. Johnson, Jennifer A. Wargo. Gut microbiota-driven alterations in tumor immunity can modulate the growth of metastatic brain tumors [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P018.