研究动态
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肿瘤生物力学作为一种新型成像生物标志物,用于评估小鼠神经胶质瘤模型对免疫治疗的反应。

Tumor biomechanics as a novel imaging biomarker to assess response to immunotherapy in a murine glioma model.

发表日期:2024 Jul 06
作者: Yannik Streibel, Michael O Breckwoldt, Jessica Hunger, Chenchen Pan, Manuel Fischer, Verena Turco, Berin Boztepe, Hannah Fels-Palesandro, Jonas G Scheck, Volker Sturm, Kianush Karimian-Jazi, Dennis A Agardy, Giacomo Annio, Rami Mustapha, Shreya S Soni, Abdulrahman Alasa, Ina Weidenfeld, Christopher B Rodell, Wolfgang Wick, Sabine Heiland, Frank Winkler, Michael Platten, Martin Bendszus, Ralph Sinkus, Katharina Schregel
来源: Brain Structure & Function

摘要:

胶质母细胞瘤是最常见、最具侵袭性的原发性恶性脑肿瘤,预后较差。目前正在研究新的免疫治疗方法。尽管磁共振成像 (MRI) 是治疗监测最重要的成像工具,但疗效评估常常受到治疗相关组织变化的阻碍。由于肿瘤和治疗相关的组织反应在结构上有所不同,我们假设生物力学可能是分化的相关成像指标。采用纵向 MRI 和磁共振弹性成像 (MRE) 来监测原位同基因实验性神经胶质瘤对 Toll 样受体 7/8 激动剂免疫治疗的反应。成像结果与组织学和光片显微镜数据相关。在这里,我们通过量化反应相关肿瘤力学的变化,将 MRE 确定为一种有前景的免疫治疗监测非侵入性成像方法。具体来说,我们表明,与未治疗的肿瘤相比,治疗后的肿瘤相对软化与治疗诱导的肿瘤相关骨髓细胞再教育后的炎症过程有关。从机制上讲,免疫治疗后骨髓流入和炎症(包括细胞外基质降解)的综合作用构成了治疗后的肿瘤比未治疗的神经胶质瘤更软的基础。这是治疗反应优于肿瘤体积等既定成像指标的早期指标。整体抗肿瘤炎症过程可能对人脑组织生物力学产生类似的影响,这使得 MRE 成为一种很有前景的工具,可用于早期评估神经胶质瘤患者对免疫治疗的反应,从而强烈影响患者的治疗路径。© 2024。作者。
Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.© 2024. The Author(s).