Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments.
Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments.
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DOI：
10.3390/cells10113155
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发表时间：
2021-11-13
期刊：
影响因子：
6
通讯作者：
Bankert RB
中科院分区：
文献类型：
--
作者：
Shenoy GN;Bhatta M;Bankert RB
外泌体是细胞外囊泡（EV）的一个子集，其由细胞释放并发挥多种生理作用，包括调节免疫系统。外来体是异质的，并且大量存在于肿瘤微环境中。这些囊泡的一个大的子集已被证明是免疫抑制。在这篇综述中，我们专注于外泌体在人类肿瘤微环境中对T细胞功能的抑制。我们首先简要介绍外泌体，重点是它们的生物起源，分离和表征。接下来，我们讨论了外泌体对T细胞的免疫抑制作用，回顾了体外研究，证明了已知与外泌体介导的T细胞功能抑制相关的不同蛋白质、核酸和脂质的作用。在这里，我们还讨论了初步的原理验证研究，这些研究确定了通过阻断或靶向外泌体来拯救T细胞功能的潜力。在最后一节中，我们回顾了用于研究以及靶向外泌体介导的免疫抑制的不同体内模型，突出了在最近的一项研究中以评估新型磷脂酰丝氨酸结合分子靶向免疫抑制性肿瘤相关外泌体的功效为特征的拟异种小鼠（X小鼠）模型和网膜肿瘤异种移植物（OTX）模型。
Exosomes are a subset of extracellular vesicles (EVs) that are released by cells and play a variety of physiological roles including regulation of the immune system. Exosomes are heterogeneous and present in vast numbers in tumor microenvironments. A large subset of these vesicles has been demonstrated to be immunosuppressive. In this review, we focus on the suppression of T cell function by exosomes in human tumor microenvironments. We start with a brief introduction to exosomes, with emphasis on their biogenesis, isolation and characterization. Next, we discuss the immunosuppressive effect of exosomes on T cells, reviewing in vitro studies demonstrating the role of different proteins, nucleic acids and lipids known to be associated with exosome-mediated suppression of T cell function. Here, we also discuss initial proof-of-principle studies that established the potential for rescuing T cell function by blocking or targeting exosomes. In the final section, we review different in vivo models that were utilized to study as well as target exosome-mediated immunosuppression, highlighting the Xenomimetic mouse (X-mouse) model and the Omental Tumor Xenograft (OTX) model that were featured in a recent study to evaluate the efficacy of a novel phosphatidylserine-binding molecule for targeting immunosuppressive tumor-associated exosomes.
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