Downregulation of IRF8 in Alveolar Macrophages by G-CSF Promotes Metastatic Tumor Progression

Authors

Stephanie L Tzetzo
Elliot D Kramer
Hemn Mohammadpour
Minhyung Kim
Spencer R Rosario
Han Yu
Melissa R Dolan
Chetan C Oturkar
Brian G Morreale
Paul N Bogner
Aimee B Stablewski
Fernando J Benavides
Craig M Brackett
John M L Ebos
Gokul M Das
Mateusz Opyrchal
Michael J Nemeth
Sharon S Evans
Scott I Abrams

Publication Date

3-15-2024

Journal

iScience

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

Keywords

Microenvironment, Immunology, Cancer

Comments

Supplementary Materials

PMID: 38420590