RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Implications of glioblastoma-derived exosomes in modifying the immune system: state-of-the-art and challenges.
Implications of glioblastoma-derived exosomes in modifying the immune system: state-of-the-art and challenges.
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胶质母细胞瘤是一种预后不良的脑癌。经典化疗和手术治疗的失败表明需要新的治疗方法。在无细胞方案中,外泌体是多功能的细胞外囊泡(EVs),能够携带重要货物跨越血脑屏障(BBB)等屏障到达靶细胞。这使外泌体成为治疗胶质母细胞瘤的一个有趣选择。
此外,外泌体可以包含多种治疗性货物,包括脂质、蛋白质和核酸,这些均取自其来源细胞的特定细胞间区室。暴露于各种免疫调节刺激的细胞可以产生富含特定治疗性分子的外泌体。
值得注意的是,外泌体的分泌可以改变先天性和适应性免疫系统中的免疫反应。例如,巨噬细胞摄取胶质母细胞瘤相关外泌体(GBex)可以影响巨噬细胞动态(例如,改变CD标志物表达)。GBex上关键免疫调节蛋白如细胞毒性T淋巴细胞抗原-1(CTLA1)和程序性死亡-1(PD-1)的表达表明这些纳米级囊泡与免疫系统的直接串扰。
本研究综述了外泌体在免疫系统细胞(包括B细胞、T细胞、自然杀伤(NK)细胞和树突状细胞(DCs))中的作用,以及该领域的新技术。
Glioblastoma is a brain cancer with a poor prognosis. Failure of classical chemotherapy and surgical treatments indicates that new therapeutic approaches are needed. Among cell-free options, exosomes are versatile extracellular vesicles (EVs) that carry important cargo across barriers such as the blood-brain barrier (BBB) to their target cells. This makes exosomes an interesting option for the treatment of glioblastoma.
Moreover, exosomes can comprise many therapeutic cargos, including lipids, proteins, and nucleic acids, sampled from special intercellular compartments of their origin cell. Cells exposed to various immunomodulatory stimuli can generate exosomes enriched in specific therapeutic molecules.
Notably, the secretion of exosomes could modify the immune response in innate and adaptive immune systems. For instance, glioblastoma-associated exosomes (GBex) uptake by macrophages could influence macrophage dynamics (e. g. , shifting CD markers expression).
Expression of critical immunoregulatory proteins such as cytotoxic T-lymphocyte antigen-1 (CTLA1) and programmed death-1 (PD-1) on GBex indicates the direct crosstalk of these nano-size vesicles with the immune system. The present study reviews the role of exosomes in immune system cells, including B cells, T cells, natural killer (NK) cells, and dendritic cells (DCs), as well as novel technologies in the field.
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