AUTHOR=Tian Jia-Wen , Fang Yu-Han , Zhang He-Jing , Yu Zi-Li TITLE=The dual effects of macrophage-derived extracellular vesicles on tumor cell behavior: mechanisms and clinical potential JOURNAL=Frontiers in Oncology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1586083 DOI=10.3389/fonc.2025.1586083 ISSN=2234-943X ABSTRACT=Macrophages, key players in the immune system, exhibit diverse roles in tumor progression and regulation. Macrophages release extracellular vesicles (EVs), membrane-bound particles that facilitate intercellular communication and cargo transfer. Macrophage-derived EVs (M-EVs) demonstrate a complex dual function in tumor development, with their effects dependent on their origin and the tumor microenvironment. M1-EVs show anti-tumor properties by reversing immune escape, while M2-EVs promote tumor biogenesis, invasion, metastasis, and therapeutic resistance. Tumor-associated macrophage-derived EVs (TAM-EVs) generally facilitate tumor progression but may exhibit anti-tumor characteristics in specific cancers. M-EVs, particularly M1-EVs, show promise as drug delivery vehicles in tumor-targeted therapy due to their targeting capabilities and ability to cross physiological barriers. Despite challenges in clinical application, ongoing research aims to harness the potential of M-EVs for more effective and personalized cancer treatments. This review summarizes how M-EVs influence tumor cell behavior, their mechanisms of action, and the challenges related to specificity, isolation, and clinical application. Collectively, this comprehensive analysis not only provides researchers with a better understanding of the complex roles of M-EVs in cancer biology but also lights the way for innovative therapeutic strategies, potentially advancing the development of more effective and personalized cancer treatments.