在阿尔茨海默病和其他神经退行性疾病的发病过程中，巨噬细胞特异性信号分子-髓系细胞表达的触发受体2（TREM2）起着控制小胶质细胞重要功能的作用。TREM2在不同类型癌症中的肿瘤相关巨噬细胞中也高度表达。本研究旨在探讨TREM2对胶质瘤进展的影响。我们发现，在注射GL261-EGFP胶质瘤细胞的野生型动物中，TREM2对胶质瘤生长有性别依赖性的影响。最重要的是，TREM2促进雄性动物中的胶质瘤进展而不影响雌性动物。TREM2缺失的雄性小鼠中，胶质瘤相关小胶质细胞/巨噬细胞（GAMs）积累和CD31+血管密度减少。对胶质瘤组织的转录组分析显示，TREM2缺失抑制了免疫相关基因的表达。在缺乏功能性血管化和外周免疫组分的器官片模型中，胶质瘤大小不受TREM2缺陷的影响。在人类胶质母细胞瘤切除标本中，GAMs中的TREM2表达上调。根据Cancer Genome Atlas计划（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库，TREM2的表达水平与生存率呈负相关。因此，TREM2依赖的GAMs与血管生成之间的相互作用促进了胶质瘤生长。©2023年作者、GLIA由Wiley Periodicals LLC发表。

Triggering receptor expressed on myeloid cell 2 (TREM2), a myeloid cell-specific signaling molecule, controls essential functions of microglia and impacts on the pathogenesis of Alzheimer's disease and other neurodegenerative disorders. TREM2 is also highly expressed in tumor-associated macrophages in different types of cancer. Here, we studied whether TREM2 influences glioma progression. We found a gender-dependent effect of glioma growth in wild-type (WT) animals injected with GL261-EGFP glioma cells. Most importantly, TREM2 promotes glioma progression in male but not female animals. The accumulation of glioma-associated microglia/macrophages (GAMs) and CD31+ blood vessel density is reduced in male TREM2-deficient mice. A transcriptomic analysis of glioma tissue revealed that TREM2 deficiency suppresses immune-related genes. In an organotypic slice model devoid of functional vascularization and immune components from periphery, the tumor size was not affected by TREM2-deficiency. In human resection samples from glioblastoma, TREM2 is upregulated in GAMs. Based on the Cancer Genome Atlas Program (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases, the TREM2 expression levels were negatively correlated with survival. Thus, the TREM2-dependent crosstalk between GAMs and the vasculature formation promotes glioma growth.© 2023 The Authors. GLIA published by Wiley Periodicals LLC.