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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.
AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.
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这种基于 AI 的病理组学框架为免疫分析和预后预测提供了一种稳健且可解释的工具,为胶质母细胞瘤的精准放疗和 Treg 靶向治疗策略铺平了道路。
调节性T细胞(Tregs)在异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤(GBM)中显著促进免疫抑制和治疗耐药,这是一种高度侵袭性的脑肿瘤,预后极差。
本研究开发了一种人工智能驱动的病理组学模型,用于预测接受放疗的GBM患者的Treg浸润并分层预后。利用从苏木精-伊红染色活检组织中提取的高维特征,我们通过最小冗余最大相关性和Relief算法进行特征选择后,采用梯度提升构建了病理组学评分。
该模型在多中心队列(n > 300)中展现出较强的预测性能,其中高 PS 与 Treg 水平升高和总生存期降低显著相关(TCGA:HR = 2.16;验证队列:HR = 1.706)。基因集富集分析将高 PS 与免疫逃逸通路相关联,包括 Notch 和 IL-6/JAK/STAT3 信号通路,同时 DNA 修复基因 RAD50 表达升高,提示其可能与放疗反应存在潜在关联。
Regulatory T cells (Tregs) contribute significantly to immune suppression and therapy resistance in isocitrate dehydrogenase (IDH)-wild-type glioblastoma (GBM), a highly aggressive brain tumor with poor prognosis.
In this study, we developed an artificial intelligence (AI)-powered pathomics model to predict Treg infiltration and stratify prognosis in GBM patients undergoing radiotherapy. Using high-dimensional features extracted from hematoxylin and eosin-stained biopsies, we constructed a pathomics score (PS) via gradient boosting after feature selection with Minimum Redundancy Maximum Relevance (mRMR) and Relief algorithms.
The model demonstrated strong predictive performance across multi-center cohorts (n > 300), where high PS was significantly associated with elevated Treg levels and reduced overall survival (TCGA: HR = 2.16; validation cohort: HR = 1.706). Gene set enrichment analysis linked high PS to immune-evasive pathways, including Notch and IL-6/JAK/STAT3 signaling, along with increased expression of DNA repair gene RAD50, suggesting a potential association with radiotherapy response.
This AI-based pathomics framework offers a robust and interpretable tool for immunoprofiling and outcome prediction, paving the way for precision radiotherapy and Treg-targeted therapeutic strategies in glioblastoma.
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