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REVIEW

Crosstalk between Extracellular Vesicles and the Tumor Microenvironment: Mechanistic Insights and Therapeutic Opportunities

Yaqi Xu1, Jia Zhao2, Xiaowen Mao1,*
1 State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
2 School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
* Corresponding Author: Xiaowen Mao. Email: email
(This article belongs to the Special Issue: Targeting the Tumor Microenvironment: Emerging Insights into Cancer Progression and Therapeutics)

Oncology Research https://doi.org/10.32604/or.2026.079562

Received 23 January 2026; Accepted 13 April 2026; Published online 06 May 2026

Abstract

Extracellular vesicles (EVs) are actively secreted, membrane-enclosed nanoparticles that serve as pivotal mediators of intercellular communication. They function as key mediators of intercellular communication by transporting diverse biomolecules, including proteins, nucleic acids, and metabolites. Within the tumor microenvironment, EVs drive complex cellular crosstalk and critically regulate tumor progression by remodeling the extracellular matrix, conferring drug resistance, and reprogramming immune responses. Given their natural biocompatibility, tissue tropism, and ability to cross biological barriers, EVs have emerged as promising platforms for immunotherapy, tumor vaccines and targeted drug delivery system. Moreover, the rapid expansion of EV-based clinical trials highlights their promise in precision medicine. Concurrently, the limitations associated with EV-based therapeutic strategies are critically evaluated to inform future development. This review has also detailed the importance of single-vesicle analysis, which represents a rapidly evolving frontier in EV science. Aiming to bridge the gap between mechanistic understanding and clinical practice, this review delineates the pivotal roles of EV-mediated communication in reshaping the dynamic homeostasis of the tumor microenvironment. Moreover, we provide a critical analysis of current EV-based therapeutic pipelines and their translational challenges, offering key perspectives and theoretical support for the future of precision medicine.

Graphical Abstract

Crosstalk between Extracellular Vesicles and the Tumor Microenvironment: Mechanistic Insights and Therapeutic Opportunities

Keywords

Extracellular vesicles; tumor microenvironment; intercellular crosstalk; immunotherapy; tumor vaccine

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