Budayr Omar M, Miller Brian C, Nguyen Juliane
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, Division of Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Control Release. 2025 Feb 10;378:266-280. doi: 10.1016/j.jconrel.2024.12.011. Epub 2024 Dec 16.
Small extracellular vesicles (EVs) are a diverse group of lipid-based particles that are ≤200 nm in diameter and contain an aqueous core. EVs have been shown to mediate intercellular communications between a wide array of immune cells; the downstream effects are diverse and have potential implications for the development of novel immunotherapeutic treatments. Despite a high volume of studies addressing the role EVs play in the immune system, our understanding of the crosstalk between T cells and cancer cells remains limited. Here, we discuss how EVs derived from cancer cells modulate T cell functions and conversely, how T cell derived EVs are crucial in modulating adaptive immune functions. In the context of cancer, tumor derived EVs (TD-EVs) halt T cell-mediated immunity by interfering with effector functions and enhancing regulatory T cell (Treg) functions. In contrast, EVs derived from effector T cells can serve to stimulate anticancer immunity, curbing metastasis and tumor growth. These findings highlight important aspects of how EVs can both mediate the therapeutic effects of T cells as well as impair T cell-mediated immunity. This calls for a deeper understanding of EV-mediated effects in order to advance them as next-generation therapeutics and nanocarriers.
小细胞外囊泡（EVs）是一类多样的脂质颗粒，直径≤200纳米，含有水相核心。EVs已被证明可介导多种免疫细胞之间的细胞间通讯；其下游效应多种多样，对新型免疫治疗方法的开发具有潜在意义。尽管有大量研究探讨了EVs在免疫系统中的作用，但我们对T细胞与癌细胞之间的相互作用的了解仍然有限。在这里，我们讨论癌细胞衍生的EVs如何调节T细胞功能，反之，T细胞衍生的EVs在调节适应性免疫功能中如何发挥关键作用。在癌症背景下，肿瘤衍生的EVs（TD-EVs）通过干扰效应功能和增强调节性T细胞（Treg）功能来阻止T细胞介导的免疫。相比之下，效应T细胞衍生的EVs可用于刺激抗癌免疫，抑制转移和肿瘤生长。这些发现突出了EVs如何既能介导T细胞的治疗效果又能损害T细胞介导的免疫的重要方面。这需要更深入地了解EV介导的效应，以便将其作为下一代治疗方法和纳米载体加以推进。
