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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.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mirnas-a-call-to-arms-that-shapes-the-plasticity-of-tumor-associated-macrophages-in-breast-cancer/352528/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mirnas-a-call-to-arms-that-shapes-the-plasticity-of-tumor-associated-macrophages-in-breast-cancer/352528.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why does the tumor microenvironment matter in breast cancer progression and resistance?","Question",{"text":112,"@type":113},"The TME is actively shaped by cancer into a supportive ecosystem that contributes to tumor evolution, progression, and therapeutic resistance through dynamic bidirectional dialogue.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role do tumor-associated macrophages (TAMs) play in breast cancer?",{"text":117,"@type":113},"TAMs are abundant in breast cancer and often acquire an immunosuppressive M2-like phenotype, supporting immune evasion, metastasis, and therapy resistance.",{"name":119,"@type":110,"acceptedAnswer":120},"How do microRNAs influence macrophage plasticity and tumor–immune communication?",{"text":121,"@type":113},"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.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},352528,1790153305,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":46},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","TYPE Mini Review  \nPUBLISHED 18 February 2026  \nDOI 10.3389/fimmu.2026.1792965  \nOPEN ACCESS  \nEDITED BY  \nAlessandro Palma,  \nSapienza University of Rome, Italy  \nREVIEWED BY  \nSara Pagotto,  \nUniversity of Studies G. d’Annunzio Chieti and Pescara, Italy  \nGiacomo Frati,  \nHuman Technopole, Italy  \n*CORRESPONDENCE  \nMarilena V. Iorio  \n marilena. iorio@istitutotumori. mi. it †These authors have contributed equally to this work  \nRECEIVED 21 January 2026  \nREVISED 02 February 2026  \nACCEPTED 04 February 2026  \nPUBLISHED 18 February 2026  \nCORRECTED 23 February 2026  \nCITATION  \nFogazzi V, Cosentino G, Sommariva M, Galardi A, Dell’Orto E, Pupa SM, Taccioli C and Iorio MV (2026) MiRNAs:  \na call to arms that shapes the plasticity of tumor associated macrophages in breast cancer.  \nFront. Immunol. 17:1792965 .  \ndoi: 10.3389/fimmu.2026.1792965  \nCOPYRIGHT  \n© 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) .  \nThe 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.  \nMiRNAs: a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer  \nValentina 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*†  \n1 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  \nBreast 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.  \nKEYWORDS  \nbreast cancer, immune evasion, microRNAs, tumor microenvironment, tumorassociated macrophages  \n1 Introduction  \nDespite 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","cbCairQtz8KueaQf","https://ap.wps.com/l/cbCairQtz8KueaQf","pdf",795387,"English","# Key concepts\n## Breast cancer, TME, and therapeutic resistance\n## TAM polarization and immune evasion\n## MicroRNAs as mediators of bidirectional crosstalk","[{\"question\":\"Why does the tumor microenvironment matter in breast cancer progression and resistance?\",\"answer\":\"The TME is actively shaped by cancer into a supportive ecosystem that contributes to tumor evolution, progression, and therapeutic resistance through dynamic bidirectional dialogue.\"},{\"question\":\"What role do tumor-associated macrophages (TAMs) play in breast cancer?\",\"answer\":\"TAMs are abundant in breast cancer and often acquire an immunosuppressive M2-like phenotype, supporting immune evasion, metastasis, and therapy resistance.\"},{\"question\":\"How do microRNAs influence macrophage plasticity and tumor–immune communication?\",\"answer\":\"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.\"}]","MiRNAs - a call to arms that shapes the plasticity of tumor associated macrophages in breast cancer | PDF",1790100120]