The article details the creation of a comprehensive pan-cancer human brain metastases (BrM) atlas using single-cell resolution transcriptomics, integrating data from 108 BrM samples and 111 primary tumor (PT) samples. Key findings include the identification of increased chromosomal instability (CIN) and a conserved neural-like metaprogram in malignant tumor cells (MTCs) across different cancer types. The research also reveals that the BrM microenvironment is dominated by immunosuppressive immune and stromal subsets, and the authors classify the BrM ecosystem into five distinct ecotypes associated with specific clinical characteristics. Furthermore, the study pinpoints the NECTIN2-TIGIT axis as a potential universal immune checkpoint and suggests various novel cell states and subsets as future therapeutic targets.
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