研究概要
我们的结果突显了 TMIGD2 在胶质瘤进展中的密切关联,并显示其作为免疫治疗刺激性靶点的有前景的治疗潜力。
研究思路结论见上方概要
背景
在所有类型的中枢神经系统癌症中,胶质瘤仍然是成人中最常见的原发性脑肿瘤。尽管免疫调节疗法取得了显著进展,尤其是免疫检查点抑制剂,但由于胶质瘤的耐药性,其有效性仍然受到限制。TMIGD2(含跨膜和免疫球蛋白结构域2)作为一种免疫刺激受体,在初始T细胞和大多数自然杀伤(NK)细胞上组成性表达,其发现已成为多种癌症中有吸引力的免疫治疗靶点。TMIGD2的表达谱及其在胶质瘤患者总生存期中的意义仍不清楚。
方法
在本研究中,我们首先使用癌症基因组图谱(TCGA)胶质瘤转录组数据集(667例患者)评估了TMIGD2 mRNA表达,随后在中国胶质瘤基因组图谱(CGGA)队列(693例患者)中进行验证。其次,我们在来自摩洛哥胶质瘤患者的25例石蜡包埋组织块系列中检测了TMIGD2蛋白染色。统计分析使用GraphPad Prism 8软件进行。
结果
TMIGD2 表达在星形细胞瘤、IDH-1 突变、低级别和年轻胶质瘤患者中显著更高。TMIGD2 表达于免疫细胞,并且出乎意料地表达于胶质瘤患者的肿瘤细胞。有趣的是,我们的研究表明 TMIGD2 表达与血管生成、缺氧、G2/M 检查点和上皮间质转化信号通路呈负相关。我们还证明,树突状细胞、单核细胞、NK 细胞、gd T 细胞和初始 CD8 T 细胞浸润与 TMIGD2 表达呈正相关。另一方面,Mantel-Cox 分析表明,人胶质瘤中 TMIGD2 表达增加与良好的总生存期相关。Cox 多变量分析显示,TMIGD2 是胶质瘤患者良好预后的独立预测因子。
展开英文摘要原文
METHODS
In the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.
RESULTS
TMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.
DISCUSSION: Taken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.
论文信息
- 作者
- Boulhen C、Ait Ssi S、Benthami H、Razzouki I、Lakhdar A、Karkouri M、Badou A
- 单位
- Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.Morocco
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2023