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表明 M0 巨噬细胞的组装和更恶性的神经胶质瘤表型。

indicates assembly of M0 macrophage and more malignant phenotypes of glioma.

机构信息

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Aging (Albany NY). 2020 May 12;12(9):8397-8412. doi: 10.18632/aging.103147.

Abstract

Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages (TAM) are divided into either polarized M1 or M2 phenotype depending on different regulators of polarization and pro- or anti-oncogenic roles they play. Glioma-infiltrated TAMs have been newly reported contrary to the current polarization dogma. Instead, macrophages in glioma exhibit a continuum phenotype between the M1- and M2-like TAM that resembling M0 macrophage. Here we proposed an OS (overall survival)-correlated gene () via screening with transcriptional expression levels and methylation data in two glioma databases. was found highly expressed in glioma of higher WHO grade and Mesenchymal subtype glioma, and its transcriptional level could predict OS efficiently in validation datasets. EFEMP2 exhibited a remarkable preference of intercellular expression. In vitro assay showed that EFEMP2's level in medium was closely related to glioma cells' growth. Moreover, expression level was remarkably correlated with immunological responses. M0-like macrophage as a feature of malignancy of glioblastoma revealed distinct assembly in glioma with high level of . These results revealed 's role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.

摘要

巨噬细胞介导的免疫反应在肿瘤进展中至关重要,这暗示了新的潜在有效免疫治疗靶点。肿瘤相关巨噬细胞(TAM)根据极化的不同调节剂以及它们发挥的促癌或抑癌作用分为极化的 M1 或 M2 表型。与当前的极化教条相反,新报道称浸润性胶质瘤的 TAMs 存在于 M1 样和 M2 样 TAM 之间的连续表型,类似于 M0 巨噬细胞。在这里,我们通过对两个胶质瘤数据库中的转录表达水平和甲基化数据进行筛选,提出了一个与 OS(总生存期)相关的基因()。在更高 WHO 分级和间充质型胶质瘤中,发现表达水平较高,在验证数据集中,其转录水平能够有效地预测 OS。EFEMP2 在细胞间表达上表现出明显的偏好。体外实验表明,培养基中 EFEMP2 的水平与胶质瘤细胞的生长密切相关。此外,表达水平与免疫反应显著相关。作为胶质母细胞瘤恶性特征的 M0 样巨噬细胞在高表达的胶质瘤中表现出明显的聚集。这些结果揭示了作为恶性胶质瘤潜在特征标志物的作用,它富含 M0 巨噬细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b93/7244085/405af6526103/aging-12-103147-g001.jpg

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