Brain metastases (BrMs) remain a major clinical and therapeutic challenge in patients with metastatic cancers. However, advances in our understanding of BrM have been hampered by the constrained sample size and resolution of BrM profiling studies. Here, we perform integrative single-cell RNA sequencing analysis on 108 BrM samples and 111 primary tumor (PTs) samples to investigate the characteristics and remodeling of cell states and composition across cancer lineages and subsets. Recurring and enriched features of malignant cells are increased chromosomal instability, marked proliferative and angiogenic hallmarks, and adoption of a neural-like BrM-associated metaprogram. Immunosuppressive myeloid and stromal subsets dominate the BrM tumor microenvironment, which are associated with poor prognosis and resistance to immunotherapy. Furthermore, five distinct BrM ecotypes are identified, correlating with specific histopathological patterns and clinical characteristics. This work defines hallmarks of BrM biology across cancer types and suggests that shared dependencies may exist, which may be exploited clinically.

脑转移（Brain metastases, BrMs）是晚期癌症患者预后最差的并发症之一。
尽管BrMs高度常见，但由于样本量受限、研究分辨率不足，关于其免疫微环境和细胞谱系特征的系统性认知长期滞后。

本文构建了目前为止最大规模的人类脑转移单细胞图谱（PBM），系统解析了BrMs中肿瘤细胞状态、免疫抑制模式、异质性来源与五种生态型。

Cancer Cell. 2025 Jul 14;43(7):1242-1260.e9. doi: 10.1016/j.ccell.2025.03.025. Epub 2025 Apr 10.