Downregulation of IRF8 in alveolar macrophages by G-CSF promotes metastatic tumor progression.

ABSTRACT: Tissue-resident macrophages (TRMs) are abundant immune cells within pre-metastatic sites, yet their functional contributions to metastasis remain incompletely understood. Here, we show that alveolar macrophages (AMs), the main TRMs of the lung, are susceptible to downregulation of the immune stimulatory transcription factor IRF8, impairing anti-metastatic activity in models of metastatic breast cancer. G-CSF is a key tumor-associated factor (TAF) that acts upon AMs to reduce IRF8 levels and facilitate metastasis. Translational relevance of IRF8 downregulation was observed among macrophage precursors in breast cancer and a CD68^hiIRF8^loG-CSF^hi gene signature suggests poorer prognosis in triple-negative breast cancer (

SUBMITTER: Tzetzo SL 

PROVIDER: S-EPMC10901102 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature