PDF(Pubmed)
Abstract：
Among all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.
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.
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.
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.
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.
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.
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.
摘要：
■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重大进展，特别是免疫检查点抑制剂，由于神经胶质瘤耐药，其有效性仍然受到限制。TMIGD2（跨膜和免疫球蛋白结构域2）作为一种免疫刺激受体的发现，在幼稚T细胞和大多数自然杀伤（NK）细胞上组成型表达，已成为各种癌症中具有吸引力的免疫疗法靶标。TMIGD2的表达谱及其在神经胶质瘤患者总体生存中的意义仍然未知。
■在本研究中，我们首先使用癌症基因组图谱（TCGA）神经胶质瘤转录组数据集（667例患者）评估TMIGD2mRNA表达，随后通过中国胶质瘤基因组图谱（CGGA）队列（693例患者）进行验证。其次,我们检查了摩洛哥神经胶质瘤患者的一系列25个石蜡包埋块中的TMIGD2蛋白染色。使用GraphPadPrism8软件进行统计分析。
■TMIGD2在星形细胞瘤中的表达明显更高，IDH-1突变,低档,和年轻的神经胶质瘤患者。TMIGD2在免疫细胞上表达,令人惊讶的是,胶质瘤患者的肿瘤细胞。有趣的是,我们的研究表明，TMIGD2的表达与血管生成呈负相关，缺氧,G2/M检查点,和上皮向间充质转化信号通路。我们还证明了树突状细胞，单核细胞,NK细胞,gdT细胞，和幼稚CD8T细胞浸润与TMIGD2表达呈正相关。另一方面,Mantel-Cox分析证实,在人神经胶质瘤中增加的TMIGD2表达与良好的总体存活相关。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。
■放在一起，我们的研究结果凸显了TMIGD2在神经胶质瘤进展中的重要意义,并显示了其作为免疫治疗刺激靶点的良好治疗潜力.
■在本研究中，我们首先使用癌症基因组图谱（TCGA）神经胶质瘤转录组数据集（667例患者）评估TMIGD2mRNA表达，随后通过中国胶质瘤基因组图谱（CGGA）队列（693例患者）进行验证。其次,我们检查了摩洛哥神经胶质瘤患者的一系列25个石蜡包埋块中的TMIGD2蛋白染色。使用GraphPadPrism8软件进行统计分析。
■TMIGD2在星形细胞瘤中的表达明显更高，IDH-1突变,低档,和年轻的神经胶质瘤患者。TMIGD2在免疫细胞上表达,令人惊讶的是,胶质瘤患者的肿瘤细胞。有趣的是,我们的研究表明，TMIGD2的表达与血管生成呈负相关，缺氧,G2/M检查点,和上皮向间充质转化信号通路。我们还证明了树突状细胞，单核细胞,NK细胞,gdT细胞，和幼稚CD8T细胞浸润与TMIGD2表达呈正相关。另一方面,Mantel-Cox分析证实,在人神经胶质瘤中增加的TMIGD2表达与良好的总体存活相关。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。
■放在一起，我们的研究结果凸显了TMIGD2在神经胶质瘤进展中的重要意义,并显示了其作为免疫治疗刺激靶点的良好治疗潜力.
