Tumor-educated macrophages promote cytokine-driven lung colonization in triple-negative breast cancer.

Authors

María Rosado-Sanz, Nuria Martínez-Alarcón, Michaël H Meel, Sergio Rius-Perez, Zoey J Tolboom, Carmen Salvador-Coloma, Rebeca Burgos-Panadero, Esther Coronado, Guillermina Montoliu, Eloi Casals, Anna Esteve-Codina, Francisco Ripoll, Ana Santaballa, Jaime Font de Mora

Published in

Oncoimmunology. Volume 15. Issue 1. Pages 2687381. Dec 31, 2026. Epub Jun 19, 2026.

Abstract

Triple-negative breast cancer (TNBC) remains one of the most lethal breast cancer subtypes, driven by early dissemination and resistance to therapy. Here, we reveal a macrophage-centered cytokine circuit that fuels TNBC metastasis and immune evasion. Tumor cells reprogram naïve macrophages into tumor-associated macrophages (TAMs) that secrete CCL3, CCL4, CXCL2, and IL-1β, collectively promoting epithelial-to-mesenchymal transition, migration, transendothelial invasion, and lung colonization. These TAMs, in turn, convert naïve CD4⁺ T cells into FOXP3⁺ Tregs, establishing a self-reinforcing immunosuppressive niche. Pharmacological inhibition of CCR5, CXCR2, and IL1R1 with maraviroc, navarixin, and anakinra, respectively, disrupted this cytokine axis, suppressing metastatic colonization in vivo. Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.

PMID:
42319344
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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