Musatova Oxana E, Rubtsov Yury P
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.
N.N.Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, Russia.
Front Cell Dev Biol. 2023 Mar 7;11:1060000. doi: 10.3389/fcell.2023.1060000. eCollection 2023.
Glioblastoma is the most aggressive variant of glioma, the tumor of glial origin which accounts for 80% of brain tumors. Glioblastoma is characterized by astoundingly poor prognosis for patients; a combination of surgery, chemo- and radiotherapy used for clinical treatment of glioblastoma almost inevitably results in rapid relapse and development of more aggressive and therapy resistant tumor. Recently, it was demonstrated that extracellular vesicles produced by glioblastoma (GBM-EVs) during apoptotic cell death can bind to surrounding cells and change their phenotype to more aggressive. GBM-EVs participate also in establishment of immune suppressive microenvironment that protects glioblastoma from antigen-specific recognition and killing by T cells. In this review, we collected present data concerning characterization of GBM-EVs and study of their effects on different populations of the immune cells (T cells, macrophages, dendritic cells, myeloid-derived suppressor cells). We aimed at critical analysis of experimental evidence in order to conclude whether glioblastoma-derived extracellular vesicles are a major factor in immune evasion of this deadly tumor. We summarized data concerning potential use of GBM-EVs for non-invasive diagnostics of glioblastoma. Finally, the applicability of approaches aimed at blocking of GBM-EVs production or their fusion with target cells for treatment of glioblastoma was analyzed.
胶质母细胞瘤是胶质瘤中最具侵袭性的变体,胶质瘤是一种起源于神经胶质的肿瘤,占脑肿瘤的80%。胶质母细胞瘤的特点是患者预后极差;用于胶质母细胞瘤临床治疗的手术、化疗和放疗相结合几乎不可避免地会导致快速复发,并发展出更具侵袭性和抗治疗性的肿瘤。最近有研究表明,胶质母细胞瘤(GBM-EVs)在凋亡细胞死亡过程中产生的细胞外囊泡可以与周围细胞结合,并将其表型转变为更具侵袭性。GBM-EVs还参与免疫抑制微环境的建立,该微环境可保护胶质母细胞瘤免受T细胞的抗原特异性识别和杀伤。在本综述中,我们收集了有关GBM-EVs特征及其对不同免疫细胞群体(T细胞、巨噬细胞、树突状细胞、髓源性抑制细胞)影响的现有数据。我们旨在对实验证据进行批判性分析,以得出胶质母细胞瘤衍生的细胞外囊泡是否是这种致命肿瘤免疫逃逸的主要因素的结论。我们总结了有关GBM-EVs在胶质母细胞瘤非侵入性诊断中的潜在用途的数据。最后,分析了旨在阻断GBM-EVs产生或其与靶细胞融合的方法在胶质母细胞瘤治疗中的适用性。