@article{bibcite_204226,
  keywords = {CXCL12-CXCR4 chemokine axis, breast tumorigenesis, Immune Evasion, mammary gland development, tissue-resident macrophage},
  author = {Eunmi Lee and Yibin Kang},
  title = {Macrophages in the Mammary Gland Stem Cell Niche: A Double-Edged Sword in Tissue Regeneration and Tumor Initiation.},
  abstract = {<p>Stem cell populations employ cell-intrinsic and niche-mediated mechanisms to preserve long-term self-renewal and regenerative potential. We propose that tumor-initiating cells (TICs) hijack this developmental circuitry to sustain their growth and establish an early immunosuppressive microenvironment during malignant progression. Recent work implicates CXCR4 tissue-resident macrophages (TRMs) in the mammary gland as a central orchestrator of this process. Conserved CXCL12/CXCR4-AKT-β-catenin signaling links CXCR4 TRM support of normal mammary stem cells to TIC maintenance, underscoring how developmental niches are exploited in malignancy. During tumorigenesis, aberrant CXCL12 production from tumor-associated fibroblasts promotes the expansion of CXCR4 TRMs, while CXCR4 signaling enhances ALDH1A2-dependent retinoic acid production, which induces regulatory T cells and thereby suppresses anti-tumor immunity at the earliest stages of tumor development. From this perspective, early immune evasion is not only a hallmark of cancer but also a therapeutic window. Targeting TRMs early in cancer development could delay, or even prevent, malignant initiation. More broadly, we propose that TIC-niche crosstalk constitutes a tractable vulnerability, and that incorporating TRM-directed interventions alongside conventional and immune-based therapies may shift the balance toward durable tumor control.</p>},
  year = {2026},
  journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
  volume = {48},
  pages = {e70108},
  month = {02/2026},
  issn = {1521-1878},
  doi = {10.1002/bies.70108},
  language = {eng},
}