Reale Antonia, Khong Tiffany, Spencer Andrew
Myeloma Research Group, Australian Centre for Blood Diseases, Central Clinical School, Monash University-Alfred Health, Melbourne, VIC 3004, Australia.
Malignant Haematology and Stem Cell Transplantation, Department of Haematology, Alfred Hospital, Melbourne, VIC 3004, Australia.
J Clin Med. 2022 Nov 22;11(23):6892. doi: 10.3390/jcm11236892.
Tumor cells actively incorporate molecules (e.g., proteins, lipids, RNA) into particles named extracellular vesicles (EVs). Several groups have demonstrated that EVs can be transferred to target (recipient) cells, making EVs an important means of intercellular communication. Indeed, EVs are able to modulate the functions of target cells by reprogramming signaling pathways. In a cancer context, EVs promote the formation of a supportive tumor microenvironment (TME) and (pre)metastatic niches. Recent studies have revealed that immune cells, tumor cells and their secretome, including EVs, promote changes in the TME and immunosuppressive functions of immune cells (e.g., natural killer, dendritic cells, T and B cells, monocytes, macrophages) that allow tumor cells to establish and propagate. Despite the growing knowledge on EVs and on their roles in cancer and as modulators of the immune response/escape, the translation into clinical practice remains in its early stages, hence requiring improved translational research in the EVs field. Here, we comprehensively review the current knowledge and most recent research on the roles of EVs in tumor immune evasion and immunosuppression in both solid tumors and hematological malignancies. We also highlight the clinical utility of EV-mediated immunosuppression targeting and EV-engineering. Importantly, we discuss the controversial role of EVs in cancer biology, current limitations and future perspectives to further the EV knowledge into clinical practice.
肿瘤细胞会主动将分子（如蛋白质、脂质、RNA）纳入名为细胞外囊泡（EVs）的颗粒中。多个研究小组已证明，EVs能够转移至靶（受体）细胞，这使得EVs成为细胞间通讯的一种重要方式。事实上，EVs能够通过重新编程信号通路来调节靶细胞的功能。在癌症背景下，EVs促进形成支持性的肿瘤微环境（TME）和（前）转移小生境。最近的研究表明，免疫细胞、肿瘤细胞及其分泌组（包括EVs）会促进TME的变化以及免疫细胞（如自然杀伤细胞、树突状细胞、T细胞和B细胞、单核细胞、巨噬细胞）的免疫抑制功能，从而使肿瘤细胞得以建立和增殖。尽管人们对EVs及其在癌症中的作用以及作为免疫反应/逃逸调节因子的认识不断增加，但向临床实践的转化仍处于早期阶段，因此需要在EVs领域加强转化研究。在此，我们全面综述了目前关于EVs在实体瘤和血液系统恶性肿瘤的肿瘤免疫逃逸和免疫抑制中作用的知识及最新研究。我们还强调了针对EV介导的免疫抑制靶向治疗和EV工程改造的临床应用价值。重要的是，我们讨论了EVs在癌症生物学中的争议性作用、当前的局限性以及将EVs知识转化为临床实践的未来前景。
