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:Genetically edited T-cell membrane coated AIEgen nanoparticles effectively prevents glioblastoma recurrence.
胶质母细胞瘤干细胞(GSCs)是导致胶质母细胞瘤(GBM)发生和复发的肿瘤起始细胞亚群。
胶质母细胞瘤干细胞(GSCs)是导致胶质母细胞瘤(GBM)发生和复发的肿瘤起始细胞亚群。由于血管内皮和GSCs具有不同的病理特征,同时抑制二者仍是一项挑战。在此,我们提出一种联合的全方位控制策略以实现局部光热治疗(PTT)。我们通过将基因工程T细胞膜(CM)包覆于聚集诱导发光(AIE)纳米颗粒上,设计了具有AIE特性的T细胞模拟纳米颗粒(CM@AIE NPs)。CM外壳被设计为靶向CD133和表皮生长因子受体(EGFR),这为同时靶向GBM细胞和GSCs进行肿瘤治疗提供了可能。CM@AIE NPs可作为紧密连接(TJ)调节剂触发细胞内信号级联反应,导致TJ破坏和肌动蛋白细胞骨架重排,使CM@AIE NPs能够静默穿越血脑屏障(BBB)。980 nm激发触发的PTT可完全抑制肿瘤发生和复发。CM包覆纳米技术与基因编辑技术的结合可启发进一步开发协同技术以预防GBM复发。
Glioblastoma stem cells (GSCs) are subpopulations of tumor-initiating cells responsible for glioblastoma (GBM) tumorigenesis and recurrence. Dual inhibition of vascular endothelium and GSCs is still a challenge due to their different pathological features. Here we present a combined all-in-control strategy to realize a local photothermal therapy (PTT). We designed T-cell-mimic nanoparticles with aggregation-induced emission (AIE) characteristics by coating the genetically engineered T cell membrane (CM) onto AIE nanoparticles (CM@AIE NPs). The CM shell was designed against CD133 and epidermal growth factor receptor (EGFR) which provides the possibility to target both GBM cells and GSCs for cancer therapy. CM@AIE NPs can serve as the tight junction (TJ) modulators to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to allow CM@AIE NPs to cross the blood-brain barrier (BBB) silently. The 980 nm excitation-triggered PTT can completely inhibit tumorigenesis and recurrence. The combination of CM-coating nanotechnology and genetic editing technique can inspire further development of synergetic techniques for preventing GBM recurrence.
MEMBER ACCOUNT
登录成功会直接打开下一页。