肿瘤细胞治疗研究
英文原题：Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.
Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.
高级别胶质瘤（HGGs），包括胶质母细胞瘤（GBM）和儿童弥漫性中线胶质瘤（DMGs），尽管治疗取得了进展，但仍然是高度致命的。
高级别胶质瘤（HGGs），包括胶质母细胞瘤（GBM）和儿童弥漫性中线胶质瘤（DMGs），尽管治疗取得了进展，但仍然是高度致命的。肿瘤微环境（TME），特别是细胞外基质（ECM），在肿瘤进展、免疫排斥和耐药性中起着至关重要的作用。我们对原发成人及儿童HGGs的ECM进行了全面的蛋白质组学、转录组学和病理学表征。利用细胞表面蛋白质组学、TCGA转录组学和免疫组织化学，我们识别了影响免疫浸润的关键ECM成分。我们将这些发现整合到ImmunoTar中，这是一个优先排序免疫治疗靶点的计算模型。我们的研究首次呈现了HGG ECM的深入细胞表面蛋白质组学图谱，确定了CSPG4/5、PTPRZ1、SDC1、TGFBR3、PLG和GPC2作为关键靶点。我们验证了针对ECM的CAR T细胞疗法，包括Glypican-2（GPC2），其在对抗儿童DIPG方面显示出强大疗效。这些发现突显了以ECM为重点的免疫疗法作为克服HGGs免疫抑制性TME的有前景策略，尤其是在儿童患者中。
High-grade gliomas (HGGs), including glioblastoma (GBM) and pediatric diffuse midline gliomas (DMGs), remain highly fatal despite therapeutic advances. The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a crucial role in tumor progression, immune exclusion, and drug resistance. We performed a comprehensive proteomic, transcriptomic, and pathological characterization of the ECM in primary adult and pediatric HGGs. Using cell surface proteomics, TCGA transcriptomics, and immunohistochemistry, we identified key ECM components influencing immune infiltration. We integrated these findings into ImmunoTar, a computational model prioritizing immunotherapeutic targets. Our study presents the first in-depth cell surface proteomic landscape of HGG ECM, identifying CSPG4/5, PTPRZ1, SDC1, TGFBR3, PLG, and GPC2 as key targets. We validate ECM-targeted CAR T cell therapy, including Glypican-2 (GPC2), which shows strong efficacy against pediatric DIPG. These findings highlight ECM-focused immunotherapy as a promising strategy to overcome HGGs' immunosuppressive TME, particularly in pediatric patients.
MEMBER ACCOUNT
登录成功会直接打开下一页。
