AUTHOR=Ramalingam Prasanna Srinivasan , Afzal Muhammad , Babu M. Arockia , M. M. Rekha , Sahoo Samir , Pandey Surya Nath , Ali Haider , Hussain Md Sadique , Gupta Gaurav , Mekala Janaki Ramaiah , Arumugam Sivakumar 

TITLE=Targeting cancer via macrophage-derived exosomal miRNAs: implications for tumor progression and resistance

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1683799

DOI=10.3389/fimmu.2025.1683799

ISSN=1664-3224

ABSTRACT=Recent studies on macrophages showed their contribution to tumorigenesis, progression, metastasis, and chemoresistance by influencing the local tumor microenvironment and cancer cells. Exosomes form a subset of extracellular vesicles and have played a major role in the interaction between cancer cells and macrophages. This review intends to discuss the existing literature on employing macrophage-derived exosomes as a vehicle for microRNA (miRNA) delivery in oncological applications. It will evaluate the molecular principles of this therapeutic approach and its capacity to enhance cancer therapy by elucidating problems like drug and radio-resistance. This review uniquely emphasizes the diagnostic and therapeutic potential of macrophage-derived exosomal miRNAs, summarizing current understandings into their molecular processes, tumor specificity, and strategies to overcome therapeutic resistance. This review synthesizes recent studies and evaluates how macrophage-derived exosomes and their miRNAs contribute to cancers. These vesicles are multipurpose tools that regulate tumor behavior, considering they can regulate it through post-transcriptional regulation and protein phosphorylation. Such exosomes that are engineered can potentially introduce a novel dimension because they have the capability of delivering targeted oncogenic or tumor-suppressive miRNAs to overcome limitations of current cancer therapeutics, particularly drug and radioresistance. Engineered macrophage-derived exosomes may thus have the potential as a novel approach for cancer treatment and overcoming therapeutic resistance.