@article{bibcite_204221, keywords = {bone metastasis, estrogen receptor, estrogen signaling, fatty acid, immune exclusion, macrophage, metastatic niche, niche labeling, sortase A, Tumor Microenvironment}, author = {Zhan Xu and Fengshuo Liu and Yunfeng Ding and Tianhong Pan and Yi-Hsuan Wu and Yujiao Han and Jun Liu and Igor Bado and Weijie Zhang and Ling Wu and Yang Gao and Xiaoxin Hao and Liqun Yu and Xuan Li and David Edwards and Hilda Chan and Sergio Aguirre and Michael Dieffenbach and Elina Chen and Siyue Wang and Yichao Shen and Dane Hoffman and Luis Dominguez and Charlotte Rivas and Xiang Chen and Hai Wang and Yibin Kang and Zbigniew Gugala and Robert Satcher and Xiang Zhang}, title = {Unbiased niche labeling maps immune-excluded niche in bone metastasis.}, abstract = {
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 (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. ERα$^{+}$ macrophages were also identified in human bone metastases across multiple cancer types. Together, these findings define a distinct ERα$^{+}$ macrophage niche and establish macrophage ERα signaling as a key driver of T cell exclusion during metastatic colonization.
}, year = {2026}, journal = {Cell}, volume = {189}, pages = {3287-3305.e25}, month = {05/2026}, issn = {1097-4172}, doi = {10.1016/j.cell.2026.04.009}, language = {eng}, }