Fernández-Delgado Irene, Calzada-Fraile Diego, Sánchez-Madrid Francisco
Vascular Pathophysiology Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
Immunology Service, Health Research Institute Hospital La Princesa (IIS-IP), Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain.
Cancers (Basel). 2020 Nov 28;12(12):3558. doi: 10.3390/cancers12123558.
Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules on their surface that enable the interaction with other immune cells such as CD8 T cells, and other ligands that stimulate natural killer (NK) cells, thereby instructing tumor rejection, and counteracting immune-suppressive tumor microenvironment. Malignant cells oppose this effect by secreting EVs bearing a variety of molecules that block DCs function. For instance, tumor-derived EVs (TDEVs) can impair myeloid cell differentiation resulting in myeloid-derived suppressor cells (MDSCs) generation. Hence, the unique composition of EVs makes them suitable candidates for the development of new cancer treatment approaches including prophylactic vaccine targeting oncogenic pathogens, cancer vaccines, and cancer immunotherapeutics. We offer a perspective from both cell sides, DCs, and tumor cells, on how EVs regulate the antitumor immune response, and how this translates into promising therapeutic options by reviewing the latest advancement in DEV-based cancer therapeutics.
细胞外囊泡（EVs）作为膜蛋白、胞质蛋白、脂质以及包括不同RNA在内的核酸运输载体，在细胞间通讯中发挥着关键作用。树突状细胞（DCs）衍生的细胞外囊泡（DEVs），尽管表达情况各异，但在其表面表达主要组织相容性复合体（MHC）-肽复合物和共刺激分子，能够与其他免疫细胞如CD8 T细胞相互作用，以及与刺激自然杀伤（NK）细胞的其他配体相互作用，从而指导肿瘤排斥反应，并对抗免疫抑制性肿瘤微环境。恶性细胞通过分泌携带多种阻断DCs功能分子的细胞外囊泡来对抗这种效应。例如，肿瘤来源的细胞外囊泡（TDEVs）可损害髓样细胞分化，导致髓样来源的抑制细胞（MDSCs）生成。因此，细胞外囊泡的独特组成使其成为开发新癌症治疗方法的合适候选者，包括针对致癌病原体的预防性疫苗、癌症疫苗和癌症免疫疗法。我们通过回顾基于DEVs的癌症治疗的最新进展，从细胞的两个方面，即DCs和肿瘤细胞，阐述细胞外囊泡如何调节抗肿瘤免疫反应，以及这如何转化为有前景的治疗选择。
