Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Immunol. 2022 Feb 21;13:841404. doi: 10.3389/fimmu.2022.841404. eCollection 2022.
The glioma immune microenvironment (GIM), consisting of glioma cells, stromal cells, and immune cells, accelerates the initiation, development, immune evasion, chemoresistance, and radioresistance of glioblastoma (GBM), whereas the immunosuppressive mechanisms of GBM have not been thoroughly elucidated to date. The glioma data downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to evaluate the composition of tumor-infiltrating immune cells (TICs) by the CIBERSORT algorithm. RNA-seq datasets from the TCGA and CGGA were used to analyze the relationship between immune scores with patients' characteristics and TICs, which showed higher ratios of tumor-inhibiting/tumor-promoting signatures (M2/M1 macrophages) along with higher immune scores. The distribution of TICs among different glioma patients and the correlation with hazard ratio (HR) analysis suggested that M2 macrophages were abundant in malignant gliomas and indicated an unfavorable prognosis. We further analyzed TCGA cases with available mutation and copy-number alteration information, which showed that the status of PTEN could influence the immune microenvironment of glioma patients. Tissue microarrays of 39 GBM patients were carried out to confirm the clinical significance of PTEN and macrophage markers. We found that the high expression of PTEN was associated with a more extended survival period of glioma patients, positively correlated with M2 macrophages and negatively with M1 macrophages. Transwell and flow cytometry analyses demonstrated that PTEN status could prevent M1 to M2 polarization and M2 macrophage recruitment of gliomas The newly discovered immunoregulatory activity of PTEN opens innovative avenues for investigations relevant to counteracting cancer development and progression.
胶质瘤免疫微环境（GIM）由胶质瘤细胞、基质细胞和免疫细胞组成，加速了胶质母细胞瘤（GBM）的发生、发展、免疫逃逸、化疗耐药和放疗耐药，而 GBM 的免疫抑制机制尚未得到充分阐明。从癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库下载的胶质瘤数据用于通过 CIBERSORT 算法评估肿瘤浸润免疫细胞（TIC）的组成。来自 TCGA 和 CGGA 的 RNA-seq 数据集用于分析免疫评分与患者特征和 TICs 之间的关系，结果表明肿瘤抑制/促进标志物（M2/M1 巨噬细胞）的比例较高，同时免疫评分较高。不同胶质瘤患者之间 TICs 的分布以及与风险比（HR）分析的相关性表明，M2 巨噬细胞在恶性胶质瘤中丰富，预示着预后不良。我们进一步分析了具有可用突变和拷贝数改变信息的 TCGA 病例，结果表明 PTEN 的状态可以影响胶质瘤患者的免疫微环境。对 39 名 GBM 患者的组织微阵列进行了分析，以证实 PTEN 和巨噬细胞标志物的临床意义。我们发现，PTEN 的高表达与胶质瘤患者的生存周期延长相关，与 M2 巨噬细胞呈正相关，与 M1 巨噬细胞呈负相关。Transwell 和流式细胞术分析表明，PTEN 状态可以阻止 M1 向 M2 极化和 M2 巨噬细胞募集胶质瘤。PTEN 的新发现的免疫调节活性为研究对抗癌症发展和进展提供了创新途径。
