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外泌体与分泌:作用机制?

Exosome and Secretion: Action On?

机构信息

Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200093, China.

Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

出版信息

Adv Exp Med Biol. 2020;1248:455-483. doi: 10.1007/978-981-15-3266-5_19.

Abstract

Originally treated as part of a cellular waste, extracellular vesicles (EVs) are being shown to possess a vast variety of functions, of which exosome is the most studied one. Most cells, such as tumor cells, immunocytes, and fibroblasts can secrete exosomes, especially under certain stresses the amount is much higher, and the contents of exosome represent the status of the donor cells and the tumor microenvironment. As crucial transporters for cells' content exchange, much attention has been raised in the utilities of exosomes to suppress immune response, and to modify a microenvironment favorable for cancer progression. Exosomal immune checkpoints, such as programmed cell death ligand 1 (PD-L1), contribute to immunosuppression and are associated with anti-PD-1 response. Many forms of soluble immune checkpoint receptors have also been shown to influence efficacy mediated by their therapeutic antibodies. Therefore, targeting pro-tumorous exosomes may achieve antitumor effect supplementary to existing therapies. Exosome, itself natural liposome-like structure, allows it to be a potential drug delivery tool.

摘要

最初被视为细胞废物的一部分,细胞外囊泡 (EVs) 被证明具有多种功能,其中外泌体是研究最多的一种。大多数细胞,如肿瘤细胞、免疫细胞和成纤维细胞,都可以分泌外泌体,特别是在某些应激下,外泌体的数量会更高,而外泌体的内容代表了供体细胞和肿瘤微环境的状态。作为细胞内容物交换的关键载体,外泌体在抑制免疫反应和修饰有利于癌症进展的微环境方面的应用引起了广泛关注。外泌体免疫检查点,如程序性细胞死亡配体 1(PD-L1),有助于免疫抑制,并与抗 PD-1 反应相关。许多形式的可溶性免疫检查点受体也被证明会影响其治疗性抗体介导的疗效。因此,针对促瘤性外泌体可能会在现有治疗方法的基础上实现抗肿瘤作用。外泌体本身具有类似于天然脂质体的结构,使其成为一种有潜力的药物递送工具。

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