Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-02-28 DOI:10.1016/j.celrep.2025.115356

Samantha M Golomb, Ian H Guldner, Emilija Aleksandrovic, Shaneann R Fross, Xiyu Liu, Lu Diao, Karena Liang, Jinxuan Wu, Qingfei Wang, Jacqueline A Lopez, Siyuan Zhang

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引用次数: 0

Abstract

Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.

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转移癌细胞与脑部微环境之间的相互作用调控着脑转移（BrMet）的进展。中枢神经系统（CNS）本地和外周免疫细胞影响着脑转移瘤的免疫环境，但调节这种微环境的动态和因素仍不清楚。由于肠道微生物群会影响中枢神经系统和外周免疫活动，我们研究了它在整个 BrMet 阶段调节免疫反应动态的作用。抗生素诱导的（ABX）肠道菌群失调显著增加了BrMet的负担，但粪便移植后则与对照组持平，这凸显了微生物组多样性是BrMet的调节因子。单细胞测序显示，在这两种情况下，BrMet 的发展过程中都存在高度动态的免疫景观。然而，单核细胞炎症反应的时间发生了改变。在ABX处理的小鼠中，小胶质细胞在晚期转移中显示出更高的激活特征。对 T 细胞和小胶质细胞的扰动表明，在肠道菌群失调的情况下，这些细胞类型参与了对 BrMet 的调节。这些数据表明，肠道菌群失调对整个BrMet进展过程中的免疫反应动态产生了深远影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.