Extracellular vesicles and acetylation: reciprocal regulation in disease progression

Extracellular vesicles (EVs) are membrane-bound particles secreted by diverse cell types and mediate intercellular communication through the transfer of proteins, RNAs, lipids, metabolites and other biomolecules. EVs participate in multiple physiological and pathological processes, including immune regulation, tumor progression, metastasis, neurodegenerative disorders and cardiovascular disease. Acetylation is a dynamic post-translational and epigenetic modification that regulates protein function, chromatin accessibility, transcription, metabolism and immune responses. Emerging evidence indicates a bidirectional regulatory relationship between EVs and acetylation. Acetylation can regulate EV biogenesis, cargo loading, secretion and EV-associated protein trafficking, whereas EVs can reshape intracellular acetylation states in recipient cells by transferring non-coding RNAs, proteins, metabolites and acetylated proteins. In this review, we summarize the mechanisms by which acetylation controls EV generation and cargo composition, and how EVs, in turn, modulate acetyl-CoA metabolism, acetylation writers and erasers, and acetylated protein signaling in recipient cells. Given the relevance of this axis to cancer immunity, we also discuss its implications for antigen presentation, macrophage polarization, CD8⁺ T-cell dysfunction, regulatory T cells, natural killer cells and immune checkpoint regulation. Furthermore, we evaluate the biomarker potential of EV-associated acetylation signatures, the therapeutic relevance of histone deacetylase inhibitors and EV-based interventions, and the current methodological and translational limitations of the field. This review provides a conceptual framework for understanding the EV-acetylation axis in disease progression and highlights future directions for immunological, biomarker and therapeutic development.