Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.
Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.
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基于机器学习的 SOX10 鉴定作为神经胶质瘤巨噬细胞的免疫调节剂
DOI：
10.3389/fimmu.2022.1007461
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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神经胶质瘤起源于神经胶质细胞，是中枢神经系统中最致命的原发性肿瘤。像手术这样的标准治疗并没有显著改善胶质母细胞瘤患者的预后。近年来，免疫治疗已成为一种新颖而有效的选择。Sry型HMG盒（SOX）家族作为一组保守的转录调控因子，已被证实与多种疾病相关。基于大规模的机器学习，我们发现SOX家族具有显著的免疫特征和基因组特征，在胶质瘤中可以分为两个不同的簇，其中SOX 10被鉴定为胶质瘤中巨噬细胞的优秀免疫调节剂。SOX 10的高表达与LGG、HGG和泛癌组中较短的OS相关，但受益于免疫治疗。在单细胞测序中发现，SOX 10在神经元、M1巨噬细胞和神经干细胞中含量很高。此外，发现巨噬细胞在SOX 10高表达组中升高。SOX 10与巨噬细胞产生细胞因子呈正相关，对巨噬细胞的趋化和迁移有负调节作用。总之，我们的研究表明SOX家族具有突出的聚集能力，表明SOX 10是胶质瘤中巨噬细胞的免疫调节剂，可以成为胶质瘤免疫治疗的有效靶点。
Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages’ chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.