The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer
Yang Ou
Abstract
mice, and their tumor suppressive effects were weakened. Mechanistically, Zeb1 played a crucial role in transcriptionally promoting the production of Cxcl1 in tumor cells. In turn, Cxcl1 activated the Cxcr2-Jak-Stat3 pathway to induce M2 polarization of TAMs in a paracrine manner, which eventually led to T-cell inactivation and impaired the antitumor immune response in breast cancer. Our results collectively revealed an important role of Zeb1 in remodeling the tumor microenvironment, suggesting a novel therapeutic intervention for the treatment of advanced breast cancer.
Topics & Concepts
CXCL1Cancer researchImmune systemMacrophage polarizationBreast cancerMedicineMacrophageCancerImmunologyChemistryInternal medicineChemokineIn vitroBiochemistryImmune cells in cancerImmunotherapy and Immune ResponsesMicroRNA in disease regulation