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:EV-Mediated Oncogenic Regulation in Lung Cancer and Clinical Translation: From Liquid Biopsy to Targeted Delivery Systems.
肺癌(LC)仍然是全球癌症相关死亡的主要原因。
肺癌(LC)仍是全球癌症相关死亡的首要原因。延迟诊断、治疗耐药和术后高复发率是损害其临床结局的主要障碍。细胞外囊泡(EVs)是细胞分泌的纳米级脂质囊泡,通过传递核酸和蛋白质等生物活性货物介导细胞间通讯。在肺癌微环境中,EVs 重塑包括 PI3K/AKT 和 NF-κB 在内的核心信号轴,进而驱动标志性恶性表型:血管生成、远处转移、免疫逃逸和多药耐药。凭借强大的理化稳定性、完整的分子货物特征以及微创采样的可行性,EVs 成为液体活检的理想肿瘤生物标志物。此外,其固有的低免疫原性使 EVs 成为多功能纳米载体,能够放大常规放疗、化疗和免疫治疗所引发的抗肿瘤效应。然而,显著的固有异质性、EVs 分离与表征缺乏统一标准、规模化生产的障碍以及肿瘤靶向效率不足,共同阻碍了其临床转化。本综述系统剖析了 EVs 调控肺癌恶性进展的分子机制,全面概述了 EVs 在基于液体活检的早期筛查、预后分层、靶向药物递送和细胞免疫治疗中的应用的最新进展,深入讨论了当前存在的转化瓶颈,并展望了 EVs 在肺癌精准肿瘤学中的未来方向。该工作为开发下一代以 EV 为核心的诊断和治疗平台提供了理论指导。
Lung cancer (LC) remains the leading cause of cancer-associated mortality globally. Delayed diagnosis, therapeutic resistance and high postoperative recurrence are major hurdles that compromise its clinical outcomes. Extracellular vesicles (EVs) are cell-secreted nanoscale lipid vesicles that mediate intercellular crosstalk via the transfer of bioactive cargo, such as nucleic acids and proteins. In the lung cancer microenvironment, EVs remodel core signaling axes including PI3K/AKT and NF-κB, consequently driving hallmark malignant phenotypes: angiogenesis, distant metastasis, immune evasion and multidrug resistance. Boasting robust physicochemical stability, complete molecular cargo signatures and minimally invasive sampling feasibility, EVs represent ideal tumor biomarkers for liquid biopsy. Additionally, their intrinsic low immunogenicity renders EVs versatile nanovehicles capable of amplifying anti-tumor effects elicited by conventional radiotherapy, chemotherapy and immunotherapy. However, substantial inherent heterogeneity, a lack of unified standards for EVs isolation and characterization, obstacles to scalable production and inadequate tumor-targeting efficiency collectively impede their clinical translation. This review systematically dissects the molecular mechanisms through which EVs orchestrate lung cancer malignant progression, comprehensively outlines state-of-the-art progress of EVs applications in liquid biopsy-based early screening, prognostic stratification, targeted drug delivery and cellular immunotherapy, thoroughly discusses prevailing translational bottlenecks, and envisions future directions of EVs in precision oncology for lung cancer. The work offers theoretical guidance for developing next-generation EV-centric diagnostic and therapeutic platforms.
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