MiRNAs - a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer

Sep 22, 2026

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Breast cancer remains a major cause of cancer-related mortality, driven in part by tumor microenvironment (TME) contributions to progression and therapy resistance. Tumors actively reprogram the TME into a supportive ecosystem, with tumor-associated macrophages (TAMs) frequently adopting an immunosuppressive M2-like phenotype that promotes immune evasion, metastasis, and treatment failure. MicroRNAs, exchanged via extracellular vesicles, coordinate bidirectional communication by reshaping macrophage function and sustaining cancer cell progression. Clinical miRNA modulation offers prospects for TAM reprogramming and prognostic biomarker use.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Key concepts

Breast cancer, TME, and therapeutic resistance

TAM polarization and immune evasion

MicroRNAs as mediators of bidirectional crosstalk

TYPE Mini Review PUBLISHED 18 February 2026 DOI 10.3389/fimmu.2026.1792965 OPEN ACCESS EDITED BY Alessandro Palma, Sapienza University of Rome, Italy REVIEWED BY Sara Pagotto, University of Studies G. d’Annunzio Chieti and Pescara, Italy Giacomo Frati, Human Technopole, Italy *CORRESPONDENCE Marilena V. Iorio marilena. iorio@istitutotumori. mi. it †These authors have contributed equally to this work RECEIVED 21 January 2026 REVISED 02 February 2026 ACCEPTED 04 February 2026 PUBLISHED 18 February 2026 CORRECTED 23 February 2026 CITATION Fogazzi V, Cosentino G, Sommariva M, Galardi A, Dell’Orto E, Pupa SM, Taccioli C and Iorio MV (2026) MiRNAs: a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer. Front. Immunol. 17:1792965 . doi: 10.3389/fimmu.2026.1792965 COPYRIGHT © 2026 Fogazzi, Cosentino, Sommariva, Galardi, Dell’Orto, Pupa, Taccioli and Iorio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. MiRNAs: a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer Valentina Fogazzi 1, Giulia Cosentino 1, Michele Sommariva 1,2, Angela Galardi 1, Elisa Dell’Orto 1, Serenella M. Pupa 1, Cristian Taccioli 3,4† and Marilena V. Iorio 1*† 1 Microenvironment and Biomarkers of Solid Tumors Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy, 2 Department of Biomedical Sciences for Health, University of the Study of Milan, Milan, Italy, 3 Department of Animal Medicine, Production and Health, University of Padova, Padua, Italy, 4 Department of Computer Science and Technology, University of Cambridge, Cambridge, United Kingdom Breast cancer (BC) remains a leading cause of cancer-related mortality, and a major contribution to tumor progression and resistance to therapies arise from tumor microenvironment (TME) . Tumor is indeed able to shape a self-permissive TME, reprogramming the cellular components into allies. Tumor-associated macrophages (TAMs), abundant in BC T ME, mainly acquire an immunosuppressive M2-like phenotype able to fuel tumor progression, immune evasion, metastasis and therapy resistance through a dynamic crosstalk with cancer cells. MicroRNAs, transferred via extracellular vesicles and exploited by the tumor to mold an immunesuppressive niche, act as central mediators of this bidirectional communication: tumor-derived miRNAs can reprogram macrophages toward an M2-like functional program, and TAMderived miRNAs in turn promote and sustain cancer cell progression. This miRNA-orchestrated plasticity highlights TAMs as key TME regulators. Clinically, miRNA modulation offers promising strategies forTAM reprogramming, alongside their utility as prognostic biomarkers . Integrating miRNA-targeted TME interventions with conventional therapies holds the potential to overcome resistance in high-TAM BC subtypes. KEYWORDS breast cancer, immune evasion, microRNAs, tumor microenvironment, tumorassociated macrophages 1 Introduction Despite major breakthroughs in therapeutic strategies, breast cancer (BC) remains the leading cause of cancer-related death among women worldwide (1, 2) . BC is a highly heterogeneous disease classiﬁed into distinct intrinsic molecular subtypes based on hormone receptors (ER and PR), and Human Epidermal Growth Factor Receptor 2 (HER2) expression: Luminal A, Luminal B, HER2-enriched, and Basal-like mainly represented by triple-negative breast cancer (TNBC) (3–5) . Personalized treatment approaches have dramatically improve

FAQs

Why does the tumor microenvironment matter in breast cancer progression and resistance?

The TME is actively shaped by cancer into a supportive ecosystem that contributes to tumor evolution, progression, and therapeutic resistance through dynamic bidirectional dialogue.

What role do tumor-associated macrophages (TAMs) play in breast cancer?

TAMs are abundant in breast cancer and often acquire an immunosuppressive M2-like phenotype, supporting immune evasion, metastasis, and therapy resistance.

How do microRNAs influence macrophage plasticity and tumor–immune communication?

MicroRNAs transferred via extracellular vesicles mediate bidirectional signaling: tumor-derived miRNAs can reprogram macrophages toward an M2-like program, while TAM-derived miRNAs promote and sustain cancer cell progression.

Sep 22, 2026

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