Stahl David, Knoll Rainer, Gentles Andrew J, Vokuhl Christian, Buness Andreas, Gütgemann Ines
Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.
Department I of Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany.
Cancers (Basel). 2021 Feb 18;13(4):854. doi: 10.3390/cancers13040854.
Pediatric tumors frequently arise from embryonal cells, often displaying a stem cell-like ("small round blue") morphology in tissue sections. Because recently "stemness" has been associated with a poor immune response in tumors, we investigated the association of prognostic gene expression, stemness and the immune microenvironment systematically using transcriptomes of 4068 tumors occurring mostly at the pediatric and young adult age. While the prognostic landscape of gene expression (PRECOG) and infiltrating immune cell types (CIBERSORT) is similar to that of tumor entities occurring mainly in adults, the patterns are distinct for each diagnostic entity. A high stemness score (mRNAsi) correlates with clinical and morphologic subtype in Wilms tumors, neuroblastomas, synovial sarcomas, atypical teratoid rhabdoid tumors and germ cell tumors. In neuroblastomas, a high mRNAsi is associated with shortened overall survival. In Wilms tumors a high mRNAsi correlates with blastemal morphology, whereas tumors with predominant epithelial or stromal differentiation have a low mRNAsi and a high percentage of M2 type macrophages. This could be validated in Wilms tumor tissue ( = 78). Here, blastemal areas are low in M2 macrophage infiltrates, while nearby stromal differentiated areas contain abundant M2 macrophages, suggesting local microanatomic regulation of the immune response.
儿科肿瘤常起源于胚胎细胞，在组织切片中通常呈现出干细胞样（“小圆蓝”）形态。由于最近“干性”与肿瘤中不良免疫反应相关，我们使用主要发生在儿童和青年时期的4068个肿瘤的转录组，系统地研究了预后基因表达、干性与免疫微环境之间的关联。虽然基因表达的预后格局（PRECOG）和浸润免疫细胞类型（CIBERSORT）与主要发生在成人中的肿瘤实体相似，但每种诊断实体的模式都不同。高干性评分（mRNAsi）与肾母细胞瘤、神经母细胞瘤、滑膜肉瘤、非典型畸胎样横纹肌样肿瘤和生殖细胞肿瘤的临床和形态学亚型相关。在神经母细胞瘤中，高mRNAsi与总生存期缩短相关。在肾母细胞瘤中，高mRNAsi与胚芽形态相关，而主要为上皮或间质分化的肿瘤mRNAsi低且M2型巨噬细胞百分比高。这在肾母细胞瘤组织（n = 78）中得到了验证。在这里，胚芽区域M2巨噬细胞浸润少，而附近的间质分化区域含有丰富的M2巨噬细胞，提示免疫反应的局部微解剖学调节。
