Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma
Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma
复制标题
免疫基因组分析揭示 LGALS1 有助于神经胶质瘤的免疫异质性和免疫抑制
DOI：
10.1002/ijc.32102
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发表时间：
2019-07-15
影响因子：
6.4
通讯作者：
Cai, Jinquan
中科院分区：
文献类型：
--
作者：
Chen, Qun;Han, Bo;Cai, Jinquan
肿瘤细胞与周围微环境之间的相互作用和动态通讯加速了胶质母细胞瘤的发生、发展、化疗耐药和免疫逃避。然而，到目前为止，GBM的免疫抑制机制还没有完全阐明。我们招募了六个微环境特征来识别胶质瘤微环境基因。通过SSGSEA、Estimate算法、基因本体论、通径分析等功能丰富分析，发现微环境基因的潜在功能。通过体内和体外实验验证LGALS1在GBM中的免疫功能。我们从胶质瘤数据库中筛选了8个胶质瘤微环境基因，发现在胶质瘤微环境基因中一个关键的免疫抑制基因(编码Galectin-1的LGALS1)具有明显的预后意义。具有不同LGALS1表达的胶质瘤具有特定的基因组变异谱。免疫抑制是LGALS1高表达的GBM的主要特征。LGALS1基因敲除通过下调M2巨噬细胞和髓源性抑制细胞(MDSCs)，抑制免疫抑制细胞因子，重塑GBM免疫抑制微环境。因此，我们的结果提示微环境调节在胶质瘤恶性过程中起着重要作用，并为LGALS1在胶质瘤免疫抑制环境中的作用提供了证据，靶向LGALS1可以重塑胶质瘤的免疫抑制微环境。
Mutualistic and dynamic communication between tumour cells and the surrounding microenvironment accelerates the initiation, progression, chemoresistance and immune evasion of glioblastoma (GBM). However, the immunosuppressive mechanisms of GBM has not been thoroughly elucidated to date. We enrolled six microenvironmental signatures to identify glioma microenvironmental genes. The functional enrichment analysis such as ssGSEA, ESTIMATE algorithm, Gene Ontology, Pathway analysis is conducted to discover the potential function of microenvironmental genes. In vivo and in vitro experiments are used to verify the immunologic function of LGALS1 in GBM. We screen eight glioma microenvironmental genes from glioma databases, and discover a key immunosuppressive gene (LGALS1 encoding Galectin‐1) exhibiting obviously prognostic significance among glioma microenvironmental genes. Gliomas with different LGALS1 expression have specific genomic variation spectrums. Immunosuppression is a predominate characteristic in GBMs with high expression of LGALS1. Knockdown of LGALS1 remodels the GBM immunosuppressive microenvironment by down regulating M2 macrophages and myeloid‐derived suppressor cells (MDSCs), and inhibiting immunosuppressive cytokines. Our results thus implied an important role of microenvironmental regulation in glioma malignancy and provided evidences of LGALS1 contributing to immunosuppressive environment in glioma and that targeting LGALS1 could remodel immunosuppressive microenvironment of glioma.