Salvalaggio Alessandro, Silvestri Erica, Sansone Giulio, Pinton Laura, Magri Sara, Briani Chiara, Anglani Mariagiulia, Lombardi Giuseppe, Zagonel Vittorina, Della Puppa Alessandro, Mandruzzato Susanna, Corbetta Maurizio, Bertoldo Alessandra
Department of Neuroscience, University of Padova, Padova, Italy.
Padova Neuroscience Center, University of Padova, Padova, Italy.
Front Oncol. 2022 Mar 22;12:823812. doi: 10.3389/fonc.2022.823812. eCollection 2022.
Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and peritumoral brain tissues may be measured by magnetic resonance imaging (MRI).
Pre-operative MRI was combined with immune phenotyping of intraoperative tumor tissue based on flow cytometry of myeloid cell populations that are associated with immune suppression, namely, microglia and bone marrow-derived macrophages (BMDM). These cell populations were measured from the central and marginal areas of the lesion identified intraoperatively with 5-aminolevulinic acid-guided surgery. MRI features (volume, mean and standard deviation of signal intensity, and fractality) were derived from all MR sequences (T1w, Gd+ T1w, T2w, FLAIR) and ADC MR maps and from different tumor areas (contrast- and non-contrast-enhancing tumor, necrosis, and edema). The principal components of MRI features were correlated with different myeloid cell populations by Pearson's correlation.
We analyzed 126 samples from 62 GBM patients. The ratio between BMDM and microglia decreases significantly from the central core to the periphery. Several MRI-derived principal components were significantly correlated (p <0.05, r range: [-0.29, -0.41]) with the BMDM/microglia ratio collected in the central part of the tumor.
We report a significant correlation between structural MRI clinical imaging and the ratio of recruited vs. resident macrophages with different immunomodulatory activities. MRI features may represent a novel tool for investigating the microenvironment of GBM.
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，预后不佳。关注肿瘤微环境可能为发病机制提供新的见解，但目前尚无临床工具可用于此。我们假设可通过磁共振成像（MRI）测量肿瘤和瘤周脑组织中不同白细胞群体的浸润情况。
术前MRI与术中肿瘤组织的免疫表型分析相结合，基于与免疫抑制相关的髓样细胞群体（即小胶质细胞和骨髓来源的巨噬细胞（BMDM））的流式细胞术进行分析。这些细胞群体是从术中通过5-氨基乙酰丙酸引导手术确定的病变中央和边缘区域测量的。MRI特征（体积、信号强度的平均值和标准差以及分形性）来自所有MR序列（T1w、Gd + T1w、T2w、FLAIR）和ADC MR图以及不同的肿瘤区域（对比增强和非对比增强肿瘤、坏死和水肿）。通过Pearson相关性分析，将MRI特征的主成分与不同的髓样细胞群体进行关联。
我们分析了62例GBM患者的126个样本。从中央核心到周边，BMDM与小胶质细胞的比例显著降低。几个MRI衍生的主成分与肿瘤中央部分收集的BMDM/小胶质细胞比例显著相关（p <0.05，r范围：[-0.29, -0.41]）。
我们报告了结构性MRI临床成像与具有不同免疫调节活性的募集巨噬细胞与常驻巨噬细胞比例之间的显著相关性。MRI特征可能代表一种研究GBM微环境的新工具。
