Bockmayr Michael, Mohme Malte, Klauschen Frederick, Winkler Beate, Budczies Jan, Rutkowski Stefan, Schüller Ulrich
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, Berlin, Germany.
Oncoimmunology. 2018 May 24;7(9):e1462430. doi: 10.1080/2162402X.2018.1462430. eCollection 2018.
Knowledge on immune and stromal cells in medulloblastoma microenvironment is still limited as previous work was frequently restricted by low sample size and the lack of molecular subgroup information. We characterized 10 microenvironment cell populations as well as from gene expression in 1422 brain tumors and 763 medulloblastomas. All in all, medulloblastomas showed low expression of immune markers. Still, there were substantial differences with a clustering of medulloblastoma subgroups according to their microenvironment profile. Specifically, SHH medulloblastomas displayed strong signatures of fibroblasts, T cells and macrophages, while markers of cytotoxic lymphocytes were enriched in Group 4 tumors. gene expression appeared to be relatively high in single SHH and WNT cases but was undetectable by immunohistochemistry. In addition, two diverse immuno-stromal patterns were identified, indicating distinct types of local tumor immunosuppression, which were primarily controlled by either macrophage and regulatory T cell-mediated mechanisms or immunosuppressive cytokines and checkpoints, respectively. None of the immune cell signatures had an independent prognostic value in the present dataset after multiple testing correction. These results suggest a mild, but subgroup-specific infiltration of immune cells in medulloblastoma.
由于先前的研究常常受到样本量小和缺乏分子亚组信息的限制，因此对髓母细胞瘤微环境中免疫细胞和基质细胞的了解仍然有限。我们根据1422例脑肿瘤和763例髓母细胞瘤的基因表达情况，对10种微环境细胞群进行了特征分析。总体而言，髓母细胞瘤的免疫标志物表达较低。不过，根据其微环境特征，髓母细胞瘤亚组之间仍存在显著差异。具体而言，SHH髓母细胞瘤表现出成纤维细胞、T细胞和巨噬细胞的强烈特征，而细胞毒性淋巴细胞的标志物在4组肿瘤中富集。在单个SHH和WNT病例中，[此处原文缺失相关基因名称]基因表达似乎相对较高，但免疫组化检测不到。此外，还确定了两种不同的免疫-基质模式，表明存在不同类型的局部肿瘤免疫抑制，它们分别主要由巨噬细胞和调节性T细胞介导的机制或免疫抑制细胞因子和检查点控制。在进行多次检验校正后，本数据集中没有一种免疫细胞特征具有独立的预后价值。这些结果表明，髓母细胞瘤中存在轻度但亚组特异性的免疫细胞浸润。
