Immunogenomic analysis reveals LGALS1 contributes to the immune heterogeneity and immunosuppression in glioma

被引：91

作者：

Chen, Qun ^{[1
]}

Han, Bo ^{[1
]}

Meng, Xiangqi ^{[1
]}

Duan, Chunbin ^{[1
]}

Yang, Changxiao ^{[1
]}

Wu, Zhenyu ^{[1
]}

Magafurov, Dinislam ^{[1
,2
]}

Zhao, Shihong ^{[1
]}

Safin, Shamil ^{[2
]}

Jiang, Chuanlu ^{[1
]}

Cai, Jinquan ^{[1
]}

机构：

[1] Harbin Med Univ, Heilongjiang Acad Med Sci, Neurosci Inst, Dept Neurosurg,Affiliated Hosp 2, Harbin, Heilongjiang, Peoples R China

[2] Bashkir State Med Univ, Dept Neurosurg & Med Rehabil ICPE, Ufa, Russia

来源：

INTERNATIONAL JOURNAL OF CANCER | 2019年 / 145卷 / 02期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

microenvironment; glioblastoma; LGALS1; prognosis; immunosuppression; TUMOR-ASSOCIATED MACROPHAGES; STEM-CELLS; TGF-BETA; T-CELLS; GLIOBLASTOMA; GALECTIN-1; EXPRESSION; SUPPRESSION; PROGRESSION; LYMPHOCYTES;

D O I：

10.1002/ijc.32102

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：517 / 530

页数：14

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