| First Author | Xu Z | Year | 2026 |
| Journal | Cell | Volume | 189 |
| Issue | 11 | Pages | 3287-3305.e25 |
| PubMed ID | 42054994 | Mgi Jnum | J:386125 |
| Mgi Id | MGI:8329207 | Doi | 10.1016/j.cell.2026.04.009 |
| Citation | Xu Z, et al. (2026) Unbiased niche labeling maps immune-excluded niche in bone metastasis. Cell |
| abstractText | Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERalpha) with active ERalpha signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. ERalpha(+) macrophages were also identified in human bone metastases across multiple cancer types. Together, these findings define a distinct ERalpha(+) macrophage niche and establish macrophage ERalpha signaling as a key driver of T cell exclusion during metastatic colonization. |
