Liu Yanfang, Gu Yan, Cao Xuetao
National Key Laboratory of Medical Immunology & Institute of Immunology; Second Military Medical University ; Shanghai, China.
Oncoimmunology. 2015 Apr 2;4(9):e1027472. doi: 10.1080/2162402X.2015.1027472. eCollection 2015 Sep.
Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 and CD8 T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 and CD8 Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DC-derived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.
外泌体是一种纳米级的膜泡,几乎可由包括癌细胞在内的所有类型细胞释放。作为细胞间通讯的重要介质,外泌体介导来自亲代细胞的蛋白质和遗传物质的交换。新出现的证据表明,宿主细胞或癌细胞分泌的外泌体参与肿瘤的起始、生长、侵袭和转移。此外,免疫细胞与癌细胞通过外泌体进行的通讯在调节肿瘤免疫中发挥双重作用。在本综述中,我们重点关注外泌体通过抑制免疫细胞(树突状细胞、自然杀伤细胞、CD4和CD8 T细胞等)引发的抗肿瘤反应以及诱导免疫抑制或调节性细胞群体(骨髓来源的抑制性细胞、调节性T细胞和调节性B细胞)介导的免疫抑制作用。肿瘤来源的外泌体(TEXs)传递细胞因子、微小RNA(miRNA)和功能性mRNA在免疫逃逸中至关重要。此外,几种免疫细胞(树突状细胞、CD4和CD8调节性T细胞)分泌的外泌体也参与免疫抑制。另一方面,我们总结了树突状细胞来源的和经修饰的肿瘤来源的外泌体作为肿瘤疫苗的当前应用情况。还讨论了基于外泌体的疫苗在临床应用方面的潜在挑战。