肿瘤细胞治疗研究
英文原题：Development of a Novel Extracellular Vesicle-Based Biomarker Approach for Pediatric High-Grade Glioma.
综合来看，我们的结果表明 RG 来源的 EV 可通过标志物组合进行分离和检测，为开发针对 pHGG 的新型 EV 生物标志物奠定了基础。
儿童高级别胶质瘤（pHGG）约占儿童脑肿瘤的20%，患者生存率较低。目前pHGG主要依靠MRI检出，这种检查成本高、耗时长。细胞外囊泡（EV）携带可反映其细胞来源的分子标志物，并可从多种体液中分离，因而提供了替代检测思路。近期研究显示，pHGG含有在分子和形态上类似放射状胶质细胞（RG）的细胞；RG是一类神经祖细胞。鉴于正常情况下RG仅存在于发育中的脑内，研究者提出，类RG胶质瘤细胞分泌的EV可能成为pHGG生物标志物。然而，目前尚无可特异检测RG来源EV的分子标志物。为此，研究首先筛选出一组表面标志物，用于区分类RG胶质瘤细胞来源EV与非RG细胞来源EV，随后在患者来源的细胞系中验证这些标志物的表达。对细胞培养上清中分离的EV进行分析，证实其中存在这些标志物及其他肿瘤相关标志物，包括CAR-T细胞疗法的靶点。总体而言，结果表明RG来源EV可通过这组标志物进行分离和检测，为开发基于EV的pHGG新型生物标志物奠定了基础。
Pediatric high-grade gliomas (pHGGs) account for 20% of childhood brain tumours and are associated with poor survival. Currently, pHGG detection relies on MRI, a costly and time-consuming procedure. Extracellular vesicles (EVs) carry molecular markers indicative of their cellular origin and can be isolated from various biofluids, offering an alternative approach. Recent studies showed that pHGGs contain cells that molecularly and morphologically resemble radial glia (RG), a type of neural progenitor. Given that RGs are normally exclusive to the developing brain, we hypothesized that EVs secreted from RG-like glioma cells serve as a pHGG biomarker. However, there are no established molecular markers to specifically detect RG-derived EVs. To address this, we first identified a combination of surface markers to differentiate EVs derived from RG-like glioma cells from those of non-RG cells. We next validated the expression of these markers in patient-derived cell lines. Analysis of EVs isolated from cell culture media confirmed the presence of these markers, along with other tumour-associated markers including targets of chimeric antigen receptor (CAR) T cell therapy. Taken together, our results showed that RG-derived EVs can be isolated and detected by the combination of markers, laying a groundwork for developing a novel EV-based biomarker for pHGGs.
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