CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Extracellular vesicles and miRNA-based therapies in triple-negative breast cancer: advances and clinical perspectives.
三阴性乳腺癌(TNBC)是最具侵袭性、治疗最具挑战性的亚型之一,原因在于其缺乏激素受体和人表皮生长因子受体 2(HER2)蛋白。
由于缺乏激素受体和人表皮生长因子受体2(HER2)蛋白,三阴性乳腺癌(TNBC)是最具侵袭性的亚型之一,治疗挑战巨大。发现新的分子靶点对开发TNBC特异性靶向疗法至关重要。微小RNA(miRNA)因参与细胞存活、凋亡、分化、癌变和转移等过程,已成为有前景的分子靶点。细胞外囊泡(EV)可递送miRNA、调节基因表达并支持联合治疗,因此在药物递送、免疫调节、诊断及预后生物标志物和治疗等领域受到关注。间充质干细胞来源EV(MSC-EV)可转运蛋白质、mRNA/miRNA或DNA,且其本身不能直接形成肿瘤,膜蛋白(如MHC分子)含量也较低,因此被认为是更安全的治疗选择。大量研究强调EV中的miRNA在TNBC肿瘤发生中的作用,并关注其在诊断、预后、治疗选择和监测方面的价值。然而,EV疗法,特别是MSC-EV疗法,仍处于早期发展阶段。本综述旨在讨论基于EV递送miRNA的新型治疗策略,重点关注MSC-EV作为TNBC创新肿瘤治疗方式的潜力。
Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes for treatment, due to the lack of hormone receptors and the human epidermal growth factor receptor 2 (HER2) protein. The identification of new molecular targets is important for the development of targeted and specific therapies for TNBC patients. MicroRNAs (miRNAs) have emerged as promising molecular targets, being involved in cellular processes such as cell survival, apoptosis, differentiation, carcinogenesis, and metastasis. Extracellular vesicles (EVs) have gained prominence in areas such as drug delivery, immune modulation, biomarkers for diagnosis and prognosis, and therapeutics, due to their use as vehicles for the delivery of miRNAs, regulation of gene expression, and development of combined therapeutic strategies. In particular, mesenchymal stem cell-derived EVs (MSC-derived EVs) can transfer proteins, mRNAs/miRNAs, or DNA molecules and are being considered safer treatment options due to their inability to directly form tumors and contain lower amounts of membrane proteins such as MHC molecules. Numerous studies have highlighted the role of miRNAs in EVs in TNBC tumorigenesis, with a focus on diagnosis, prognosis, treatment selection, and monitoring. However, the development of therapies with EVs, especially MSC-derived EVs, is still in its infancy. Therefore, the aim of this review is to address new therapeutic strategies based on the delivery of miRNAs through EVs, with a focus on MSC-derived EVs, for the treatment of TNBC as an innovative therapy in oncology.
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