Wang Fei, Wang Xinye, Zhang Xuehao, Hu Mengying
Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, U.S.A.
Essays Biochem. 2025 May 20. doi: 10.1042/EBC20253005.
Extracellular vesicles (EVs), secreted by all cellular organisms, are pivotal mediators of intercellular communication. By transporting biologically active cargos such as proteins, lipids, and nucleic acids, EVs facilitate transfer of molecular signals, effectively reflecting the characteristics of their parent cells. Immune cellderived EVs (iEVs) play a crucial role in the activation and regulation of both adaptive and innate immune responses. In the context of immune activation, iEVs drive immune cell development and activation, as well as enhance antigen presentation through both direct and cross-dressing mechanisms. Furthermore, iEVs act as signaling entities within immunological synapses, significantly amplifying immune response efficiency. In immune regulation, iEVs modulate the expression of immune checkpoint (IC) molecules and sustain immune homeostasis by transporting immunosuppressive cytokines and microRNAs, thereby mitigating excessive immune reactions. Nevertheless, the mechanistic underpinnings of iEV-mediated immune cell activation, antigen presentation, and immunoregulation remain inadequately explored. This review provides a comprehensive overview of the functions of iEVs from diverse immune cell origins and underlying mechanisms. It also examines cutting-edge engineering strategies targeting iEVs and their parent cells, while discussing their promising applications in oncology and immune-related diseases. These insights lay the foundation for the rational development of next-generation immunotherapies. While promising, the clinical translation of iEVs is hindered by low yield, high batch-to-batch variability, and insufficient targeting efficiency. The final section discusses key challenges and potential solutions.
细胞外囊泡（EVs）由所有细胞生物体分泌，是细胞间通讯的关键介质。通过运输蛋白质、脂质和核酸等生物活性物质，EVs促进分子信号的传递，有效反映其母细胞的特征。免疫细胞衍生的EVs（iEVs）在适应性和先天性免疫反应的激活和调节中起关键作用。在免疫激活的背景下，iEVs驱动免疫细胞的发育和激活，并通过直接和交叉着装机制增强抗原呈递。此外，iEVs作为免疫突触内的信号实体，显著提高免疫反应效率。在免疫调节中，iEVs通过运输免疫抑制细胞因子和微小RNA来调节免疫检查点（IC）分子的表达并维持免疫稳态，从而减轻过度的免疫反应。然而，iEV介导的免疫细胞激活、抗原呈递和免疫调节的机制基础仍未得到充分探索。本综述全面概述了来自不同免疫细胞来源的iEVs的功能及其潜在机制。它还研究了针对iEVs及其母细胞的前沿工程策略，并讨论了它们在肿瘤学和免疫相关疾病中的应用前景。这些见解为下一代免疫疗法的合理开发奠定了基础。尽管前景广阔，但iEVs的临床转化受到产量低、批次间差异大以及靶向效率不足的阻碍。最后一部分讨论了关键挑战和潜在解决方案。
