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
剂量异质性对微束放射治疗抗肿瘤反应的意义
英文原题：The significance of dose heterogeneity on the anti-tumor response of minibeam radiation therapy.
查看英文原题
The significance of dose heterogeneity on the anti-tumor response of minibeam radiation therapy.
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研究概要
我们的结果表明，肿瘤根除和免疫浸润均与更高的剂量异质性相关。通过优化峰值剂量以及维持最低谷剂量，实现了更高的剂量异质性。这些参数既有助于直接根除肿瘤，也有助于减少免疫抑制，这与传统质子治疗中更为免疫抑制的肿瘤环境不同，后者提供的是均匀的剂量分布。
研究思路结论见上方概要
背景
质子微束放射治疗（pMBRT）是一种基于剂量沉积强调制的非常规放射技术。由于其特定的模式，pMBRT涉及若干剂量学参数（峰剂量和谷剂量、峰谷剂量比（PVDR））和几何参数（束宽、间距），这些参数可影响生物学响应。本研究旨在为加深理解各种参数如何与核心生物学机制（特别是抗肿瘤免疫）相关联，以及这些相关性如何影响治疗结局做出贡献，目标是充分释放pMBRT的潜力。我们还评估了X射线MBRT的效果，以进一步阐明峰剂量和剂量异质性的影响。
方法
胶质母细胞瘤原位大鼠模型接受了多种pMBRT配置。研究了不同剂量学参数对生存以及对pMBRT关键机制（如免疫应答）调控的影响。后者通过免疫组织化学和流式细胞术在照射后7天进行评估。
结果
通过维持最小谷剂量以及由峰剂量驱动的高剂量异质性，各种pMBRT方案的生存率均得到改善。虽然平均剂量未影响免疫浸润，但较高的PVDR促进了免疫抑制性较低的微环境。
展开英文摘要原文
RESULTS
Survival was improved across the various pMBRT regimens via maintaining a minimum valley dose as well as a higher dose heterogeneity, which is driven by peak dose. While the mean dose did not impact immune infiltration, a higher PVDR promoted a less immunosuppressive microenvironment.
CONCLUSIONS
Our results suggest that both tumor eradication, and immune infiltration are associated with higher dose heterogeneity. Higher dose heterogeneity was achieved by optimizing the peak dose, as well as maintaining a minimum valley dose. These parameters contributed to direct tumor eradication as well as reduction of immunosuppression, which is a departure from the more immunosuppressive tumor environment found in conventional proton therapy that delivers uniform dose distributions.
论文信息
- 作者
- Potiron S、Iturri L、Juchaux M、Espenon J、Gilbert C、McGarrigle J、Ortiz Catalan R、Fernandez-Rodriguez A
- 第一作者单位
- Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France. Electronic address: sarah.potiron@curie.fr.France
- 通讯作者单位
- Institut Curie, Université PSL, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France; Université Paris-Saclay, CNRS UMR3347, Inserm U1021, Signalisation Radiobiologie et Cancer, 91400 Orsay, France. Electronic address: yolanda.prezado@curie.fr.France
- 文献类型
- 非美国政府资助研究
- 期刊
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2024 Dec
- 原文标识
- PubMed 39393469 · DOI 10.1016/j.radonc.2024.110577