Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Semin Cancer Biol. 2012 Aug;22(4):342-9. doi: 10.1016/j.semcancer.2012.02.005. Epub 2012 Feb 19.
Exosomes are endosomal-derived nanovesicles released by most cells types, including tumor cells, and principally involved in intercellular communication in physiology and disease. Tumor exosomes are gaining increasing interest in medicine and oncology as efficient tools for the delivery of defined signals. Representing the acellular replicas of tumor cells, they contain a great variety of bioactive molecules, such as proteins, RNA, miRNA and DNA. Their great ability to recirculate in body fluids and their structure allow them to transport their cargo to distant targets. Major studies have shown that tumor exosomes convey information not only between tumor cells but also to other cell types, including different immune cell components. There is increasing evidence that these nanovesicles may contribute to cancer progression by influencing different immune cell types, likely blunting specific T cell immunity and skewing innate immune cells toward a pro-tumorigenic phenotype. Because of this function and the additional property to deliver molecular signals modulating neoangiogenesis and stroma remodeling, tumor exosomes are believed to play a role in tumor progression by favoring metastatic niche onset. This review outlines the recent knowledge on immune suppressive mechanisms mediated by tumor exosomes. We will discuss our view on the role of these nanovesicular structures in cancer progression and how their presence could interfere with cancer therapy.
外泌体是大多数细胞类型(包括肿瘤细胞)释放的内体衍生的纳米囊泡,主要参与生理和疾病中的细胞间通讯。肿瘤外泌体作为传递特定信号的有效工具,在医学和肿瘤学领域越来越受到关注。作为肿瘤细胞的无细胞复制品,它们包含多种生物活性分子,如蛋白质、RNA、miRNA 和 DNA。它们在体液中循环的巨大能力及其结构使它们能够将其货物运输到远处的靶标。主要研究表明,肿瘤外泌体不仅在肿瘤细胞之间传递信息,而且还向其他细胞类型传递信息,包括不同的免疫细胞成分。越来越多的证据表明,这些纳米囊泡可能通过影响不同的免疫细胞类型而促进癌症进展,可能会削弱特定的 T 细胞免疫,并使先天免疫细胞向促肿瘤表型倾斜。由于这种功能以及传递调节新生血管形成和基质重塑的分子信号的额外特性,肿瘤外泌体被认为通过促进转移龛的发生在肿瘤进展中发挥作用。这篇综述概述了肿瘤外泌体介导的免疫抑制机制的最新知识。我们将讨论我们对这些纳米结构在癌症进展中的作用的看法,以及它们的存在如何干扰癌症治疗。