@article{204261,
  keywords = {Primary},
  author = {Eunmi Lee and Jason Hong and Gabriel Vargas and Natalie Sauerwald and Yong Wei and Xiang Hang and Chandra Theesfeld and Jean Volmar and Jennifer Miller and Wei Wang and Sha Wang and Gary Laevsky and Christina DeCoste and Yibin Kang},
  title = {CXCR4 mammary gland macrophageal niche promotes tumor initiating cell activity and immune suppression during tumorigenesis.},
  abstract = {<p>Tumor-initiating cells (TICs) share features and regulatory pathways with normal stem cells, yet how the stem cell niche contributes to tumorigenesis remains unclear. Here, we identify CXCR4 macrophages as a niche population enriched in normal mammary ducts, where they promote the regenerative activity of basal cells in response to luminal cell-derived CXCL12. CXCL12 triggers AKT-mediated stabilization of β-catenin, which induces Wnt ligands and pro-migratory genes, enabling intraductal macrophage infiltration and supporting regenerative activity of basal cells. Notably, these same CXCR4 niche macrophages regulate the tumor-initiating activity of various breast cancer subtypes by enhancing TIC survival and tumor-forming capacity, while promoting early immune evasion through regulatory T cell induction. Furthermore, a CXCR4 niche macrophage gene signature correlates with poor prognosis in human breast cancer. These findings highlight the pivotal role of the CXCL12-CXCR4 axis in orchestrating interactions between niche macrophages, mammary epithelial cells, and immune cells, thereby establishing a supportive niche for both normal tissue regeneration and mammary tumor initiation.</p>},
  year = {2025},
  journal = {Nature communications},
  volume = {16},
  pages = {4854},
  month = {05/2025},
  issn = {2041-1723},
  doi = {10.1038/s41467-025-59972-z},
  language = {eng},
}