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:Image-based models of T-cell distribution identify a clinically meaningful response to a dendritic cell vaccine in patients with glioblastoma.
Image-based models of T-cell distribution identify a clinically meaningful response to a dendritic cell vaccine in patients with glioblastoma.
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在一个尚未出现突破性疗法的领域,这些结果凸显了机器学习在增强临床试验评估、提高我们前瞻性预测患者结局的能力以及推动个体化医学追求方面的价值。
胶质母细胞瘤是一种极其异质性的肿瘤,然而当前的治疗模式却是“一刀切”的方法。数百项胶质母细胞瘤临床试验被认为失败,因为它们未能延长中位生存期,但这些队列由具有不同肿瘤的患者组成。当前评估治疗疗效的方法未能充分考虑到这种异质性。
采用基于图像的建模方法,我们从参加树突状细胞(DC)疫苗临床试验的患者的系列MRI中预测了T细胞丰度。T细胞预测在可成像肿瘤的对比增强区域和非增强区域均进行了量化,并评估了随时间的变化。
在一项DC疫苗临床试验中,一部分先前未被检测出的患者被识别为治疗响应者,并从延长的生存期中获益。在初次接种疫苗仅两个月后,响应患者的对比增强区域内模型预测的T细胞减少,同时T2/FLAIR区域增加。
Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity.
Using an image-based modeling approach, we predicted T-cell abundance from serial MRIs of patients enrolled in the dendritic cell (DC) vaccine clinical trial. T-cell predictions were quantified in both the contrast-enhancing and non-enhancing regions of the imageable tumor, and changes over time were assessed.
A subset of patients in a DC vaccine clinical trial, who had previously gone undetected, were identified as treatment responsive and benefited from prolonged survival. A mere two months after initial vaccine administration, responsive patients had a decrease in model-predicted T-cells within the contrast-enhancing region, with a simultaneous increase in the T2/FLAIR region.
In a field that has yet to see breakthrough therapies, these results highlight the value of machine learning in enhancing clinical trial assessment, improving our ability to prospectively prognosticate patient outcomes, and advancing the pursuit towards individualized medicine.
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