Department of Neurosurgery, The Third Medical Centre, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Chinese Academy of Sciences (CAS) Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2023 Mar 10;14:1097880. doi: 10.3389/fimmu.2023.1097880. eCollection 2023.
Microglia/macrophages make up the largest population of tumor-infiltrating cells. Numerous studies have demonstrated that glioma-associated microglia/macrophages (GAMs) could promote the malignant progression of gliomas in various pathways. However, the primary function of GAMs in glioma remains inconclusive. First, by the CIBERSORT algorithm, we evaluated the content of microglia/macrophages in glioma tissues by bioinformatic analysis of omic data from thousands of glioma samples. Subsequently, we analyzed and confirmed the significant relationship between GAMs and the malignant phenotype of glioma, including survival time, IDH mutation status, and time of symptom onset. Afterward, Epithelial-Mesenchymal Transition (EMT) was identified by Gene Set Enrichment Analysis (GSEA) from numerous biological processes as the most relevant mechanism of malignant progression to GAMs. Moreover, a series of clinical samples were detected, including normal brain and various-grade glioma tissues. The results not only showed that GAMs were significantly associated with gliomas and their malignancy but also that GAMs were highly correlated with the degree of EMT in gliomas. In addition, we isolated GAMs from glioma samples and constructed co-culture models () to demonstrate the promotion of the EMT process in glioma cells by GAMs. In conclusion, our study clarified that GAMs exert oncogenic effects with EMT in gliomas, suggesting the possibility of GAMs as immunotherapeutic targets.
小胶质细胞/巨噬细胞构成了肿瘤浸润细胞的最大群体。大量研究表明，胶质瘤相关的小胶质细胞/巨噬细胞（GAMs）可以通过多种途径促进胶质瘤的恶性进展。然而，GAMs 在胶质瘤中的主要功能仍不确定。首先，通过 CIBERSORT 算法，我们通过对数千个胶质瘤样本的组学数据进行生物信息学分析，评估了胶质瘤组织中小胶质细胞/巨噬细胞的含量。随后，我们分析并证实了 GAMs 与胶质瘤恶性表型之间的显著关系，包括生存时间、IDH 突变状态和症状出现时间。随后，通过基因集富集分析（GSEA），从众多生物学过程中确定上皮-间充质转化（EMT）是 GAMs 促进恶性进展的最相关机制。此外，还检测了一系列临床样本，包括正常脑组织和各种级别的胶质瘤组织。结果不仅表明 GAMs 与胶质瘤及其恶性程度显著相关，而且 GAMs 与胶质瘤中 EMT 的程度高度相关。此外，我们从胶质瘤样本中分离出 GAMs 并构建共培养模型（），以证明 GAMs 促进胶质瘤细胞的 EMT 过程。总之，我们的研究阐明了 GAMs 通过 EMT 在胶质瘤中发挥致癌作用，这表明 GAMs 作为免疫治疗靶点的可能性。
