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:Evaluating adipose-derived stem cell exosomes as miRNA drug delivery systems for the treatment of bladder cancer.
目前的结果表明,ADSC 来源的外泌体是体内小分子药物的有效递送载体,外泌体递送的 miR-138-5p 是 BC 治疗的有前景的治疗剂。
外泌体作为细胞间通讯的重要介质,在细胞间运输蛋白质和RNA。由于其具有肿瘤靶向能力、免疫兼容性、低毒性和长半衰期,间充质干细胞来源的外泌体在开发新型抗肿瘤策略方面具有巨大潜力。在此背景下,脂肪来源间充质干细胞(ADSCs)产生的外泌体在膀胱癌(BC)治疗中的作用仍不清楚。在此,我们研究了利用ADSCs作为治疗性外泌体来源的可行性,以及其在BC中递送抑癌基因miR-138-5p的功效。
通过慢病毒感染建立稳定表达miR-138-5p的ADSCs,并从细胞培养基中分离出ADSC来源的miR-138-5p外泌体(Exo-miR-138-5p)。采用伤口愈合、transwell侵袭和增殖实验在体外评估Exo-miR-138-5p对BC细胞迁移、侵袭和增殖的影响。利用皮下异种移植小鼠模型研究Exo-miR-138-5p的体内作用。
Exo-miR-138-5p在体外抑制了BC细胞的迁移、侵袭和增殖。此外,ADSC来源的外泌体能够穿透肿瘤组织,并成功递送miR-138-5p以抑制体内异种移植瘤的生长。
OBJECTIVES: Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor-targeting capacity, immune compatibility, low toxicity, and long half-life, mesenchymal stem cell-derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose-derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR-138-5p in BC. METHODS: ADSCs stably expressing miR-138-5p were established using Lentivirus infection, and ADSC-derived miR-138-5p exosomes (Exo-miR-138-5p) were isolated from the cell culture medium. The effect of Exo-miR-138-5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo-miR-138-5p was investigated using a subcutaneous xenograft mouse model. RESULTS: Exo-miR-138-5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC-derived exosomes could penetrate tumor tissues and successfully deliver miR-138-5p to suppress the growth of xenograft tumors in vivo. CONCLUSIONS: The present results reveal that ADSC-derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome-delivered miR-138-5p is a promising therapeutic agent for BC treatment.
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