Program in Molecular and Cellular Pharmacology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
Glia. 2021 Jul;69(7):1767-1781. doi: 10.1002/glia.23991. Epub 2021 Mar 11.
The characterization of the tumor microenvironment (TME) in high grade gliomas (HGG) has generated significant interest in an effort to understand how neoplastic lesions in the central nervous system (CNS) are supported and to devise novel therapeutic targets. The TME of the CNS contains unique and specialized cells, including the resident myeloid cells, microglia. Myeloid involvement in HGG, such as glioblastoma, is associated with poor outcomes. Glioma-associated microglia and infiltrating monocytes/macrophages (GAM) accumulate within the neoplastic lesion where they facilitate tumor growth and drive immunosuppression. However, it has been difficult to differentiate whether microglia and macrophages have similar or distinct roles in pathology, and if the spatial organization of these cells informs outcomes. Here, we characterize the tumor-stroma border and identify peritumoral GAM (PGAM) as a unique subpopulation of GAM. Using data mining and analyses of samples derived from both murine and human sources we show that PGAM exhibit a pro-inflammatory and chemotactic phenotype that is associated with peripheral monocyte recruitment, and decreased overall survival. PGAM act as a unique subset of GAM at the tumor-stroma interface. We define a novel gene signature to identify these cells and suggest that PGAM constitute a cellular target of the TME.
肿瘤微环境（TME）在高级别神经胶质瘤（HGG）中的特征引起了人们的极大兴趣，目的是了解中枢神经系统（CNS）中的肿瘤病变是如何得到支持的，并设计新的治疗靶点。CNS 的 TME 包含独特而专门的细胞，包括驻留的髓样细胞，小胶质细胞。髓样细胞参与 HGG（如胶质母细胞瘤）与不良预后相关。胶质瘤相关的小胶质细胞和浸润的单核细胞/巨噬细胞（GAM）在肿瘤病变内积聚，在那里它们促进肿瘤生长并驱动免疫抑制。然而，很难区分小胶质细胞和巨噬细胞在病理学中是否具有相似或不同的作用，以及这些细胞的空间组织是否会影响结果。在这里，我们描述了肿瘤-基质边界，并确定了肿瘤周围的 GAM（PGAM）为 GAM 的一个独特亚群。通过对来自鼠和人类来源的样本进行数据挖掘和分析，我们表明 PGAM 表现出促炎和趋化表型，与外周单核细胞募集和总生存期缩短有关。PGAM 在肿瘤-基质界面作为 GAM 的独特亚群发挥作用。我们定义了一个新的基因特征来识别这些细胞，并表明 PGAM 构成了 TME 的一个细胞靶标。
