Cells|Richard B. Bankert团队综述了肿瘤相关外泌体在肿瘤微环境中调控抗肿瘤T细胞的潜在治疗靶点
2022年8月4日 0条评论
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最新细胞功能及机制文献分享外泌体（Exosomes）是细胞释放的细胞外囊泡（Extracellular Vesicles，EVs）的一个子集，可发挥多种生理作用，包括调节免疫系统。2021年11月13日，美国纽约布法罗大学雅各布斯医学和生物医学科学学院微生物学和免疫学系Richard B. Bankert团队在Cells上发表了题为“Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments”的综述性论文。在本论文中，团队着重介绍了外泌体在人类肿瘤微环境中对T细胞功能抑制的作用。外泌体是异质性，在肿瘤微环境中大量存在。团队首先对外泌体进行了简要介绍，重点介绍它们的生物起源、分离和特性（图1）。接下来，讨论了外泌体对T细胞的免疫抑制作用，并回顾了已知的与外泌体介导的T细胞功能抑制相关的不同蛋白质、核酸和脂质的体外研究（图2）。此外，团队还讨论了基础性的原理研究，正是这些研究建立了阻断或靶向外泌体而调节T细胞功能的潜力。在最后一部分，团队回顾了不同的体内模型，这些模型被用来研究外泌体介导的免疫抑制，尤其是Xenomimetic小鼠（X-小鼠）模型（图3）和Omental Tumor Xenograft（OTX）模型（图4），这是最近一项评估一种新型磷脂酰丝氨酸结合分子靶向免疫抑制肿瘤相关外泌体疗效的研究特点。图1 用于表征外泌体的不同参数和方法。电子显微镜评估形态，各向异性测量检测脂质双分子层，纳米颗粒跟踪分析（NTA）分析粒度分布，流式细胞术和/或免疫印迹确定生化成分。图2 与肿瘤外泌体相关的免疫抑制分子，如蛋白质（蓝色文字）、脂质（红色文字）和核酸（绿色文字）及其对人类T细胞活化、增殖、细胞因子分泌和其他功能的影响。
图3 X-小鼠模型示意图。
图4 OTX模型示意图。期刊及DOI号Cells. 2021 Nov 13. doi: 10.3390/cells10113155.题目Tumor-Associated Exosomes: A Potential Therapeutic Target for Restoring Anti-Tumor T Cell Responses in Human Tumor Microenvironments摘要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.关键词：exosomes; T cell responses; tumor microenvironment; phosphatidylserine; PD-L1; immune checkpoints; ganglioside GD3; miRNA; FasL; xenograft models
