Abstract：
OBJECTIVE: LLT-1 is a well-known ligand for the natural killer (NK) cell inhibitory receptor NKRP1A. Here, we examined NLRC4 inflammasome components and LLT-1 expression in glioblastoma (GBM) tissues to elucidate potential associations and interactions between these factors.
METHODS: GBM tissues were collected for RNA sequencing (RNA-seq) and Immunofluorescent experiments. Colocalization of LLT-1 and other proteins was assessed by immunofluorescence. Computational analyses utilized RNA-seq data from 296 to 52 patients from the Chinese Glioma Genome Atlas and CHA medical records, respectively. These data were subjected to survival, non-negative matrix factorization clustering, Gene Ontology enrichment, and protein-protein interaction analyses. Receptor-ligand interactions between tumor and immune cells were confirmed by single-cell RNA-seq analysis.
RESULTS: In GBM tissues, LLT-1 was predominantly colocalized with glial fibrillary acidic protein (GFAP)-expressing astrocytes, but not with microglial markers like Iba-1. Additionally, LLT-1 and activated NLRC4 inflammasomes were mainly co-expressed in intratumoral astrocytes, suggesting an association between LLT-1, NLRC4, and glioma malignancy. High LLT-1 expression correlates with poor prognosis, particularly in the mesenchymal subtype, and is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. At the single-cell level, mesenchymal-like malignant cells showed high NF, NLR, and IL-1 signaling pathway enrichment compared to other malignant cell types.
CONCLUSIONS: We revealed an association between NLRC4 inflammasome activity and LLT-1 expression, suggesting a novel regulatory pathway involving TNF, inflammasomes, and IL-1, potentially offering new NK-cell-mediated anti-glioma approaches.
METHODS: GBM tissues were collected for RNA sequencing (RNA-seq) and Immunofluorescent experiments. Colocalization of LLT-1 and other proteins was assessed by immunofluorescence. Computational analyses utilized RNA-seq data from 296 to 52 patients from the Chinese Glioma Genome Atlas and CHA medical records, respectively. These data were subjected to survival, non-negative matrix factorization clustering, Gene Ontology enrichment, and protein-protein interaction analyses. Receptor-ligand interactions between tumor and immune cells were confirmed by single-cell RNA-seq analysis.
RESULTS: In GBM tissues, LLT-1 was predominantly colocalized with glial fibrillary acidic protein (GFAP)-expressing astrocytes, but not with microglial markers like Iba-1. Additionally, LLT-1 and activated NLRC4 inflammasomes were mainly co-expressed in intratumoral astrocytes, suggesting an association between LLT-1, NLRC4, and glioma malignancy. High LLT-1 expression correlates with poor prognosis, particularly in the mesenchymal subtype, and is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. At the single-cell level, mesenchymal-like malignant cells showed high NF, NLR, and IL-1 signaling pathway enrichment compared to other malignant cell types.
CONCLUSIONS: We revealed an association between NLRC4 inflammasome activity and LLT-1 expression, suggesting a novel regulatory pathway involving TNF, inflammasomes, and IL-1, potentially offering new NK-cell-mediated anti-glioma approaches.
摘要：
目的：LLT-1是众所周知的天然杀伤（NK）细胞抑制性受体NKRP1A的配体。这里,我们检测了胶质母细胞瘤(GBM)组织中NLRC4炎性体成分和LLT-1的表达,以阐明这些因子之间的潜在关联和相互作用.
方法:收集GBM组织用于RNA测序(RNA-seq)和免疫荧光实验。通过免疫荧光评估LLT-1和其他蛋白质的共定位。计算分析利用来自中国胶质瘤基因组图谱和CHA医疗记录的296至52名患者的RNA-seq数据，分别。这些数据进行了生存，非负矩阵分解聚类，基因本体富集，和蛋白质-蛋白质相互作用分析。通过单细胞RNA-seq分析证实肿瘤和免疫细胞之间的受体-配体相互作用。
结果：在GBM组织中，LLT-1主要与表达胶质纤维酸性蛋白（GFAP）的星形胶质细胞共定位，但没有像Iba-1这样的小胶质细胞标记。此外,LLT-1和活化的NLRC4炎性体主要在肿瘤内星形胶质细胞中共表达,提示LLT-1，NLRC4和神经胶质瘤恶性肿瘤之间的关联。LLT-1高表达与不良预后相关，特别是在间充质亚型中，并与TNF和NOD样受体信号通路富集有关，表明在肿瘤炎症和进展中的潜在作用。在单细胞层面,间充质样恶性细胞显示高NF，NLR,与其他恶性细胞类型相比，IL-1信号通路富集。
结论：我们揭示了NLRC4炎性体活性与LLT-1表达之间的关联，提示涉及TNF的新调节途径，炎性体,和IL-1，可能提供新的NK细胞介导的抗神经胶质瘤方法。
方法:收集GBM组织用于RNA测序(RNA-seq)和免疫荧光实验。通过免疫荧光评估LLT-1和其他蛋白质的共定位。计算分析利用来自中国胶质瘤基因组图谱和CHA医疗记录的296至52名患者的RNA-seq数据，分别。这些数据进行了生存，非负矩阵分解聚类，基因本体富集，和蛋白质-蛋白质相互作用分析。通过单细胞RNA-seq分析证实肿瘤和免疫细胞之间的受体-配体相互作用。
结果：在GBM组织中，LLT-1主要与表达胶质纤维酸性蛋白（GFAP）的星形胶质细胞共定位，但没有像Iba-1这样的小胶质细胞标记。此外,LLT-1和活化的NLRC4炎性体主要在肿瘤内星形胶质细胞中共表达,提示LLT-1，NLRC4和神经胶质瘤恶性肿瘤之间的关联。LLT-1高表达与不良预后相关，特别是在间充质亚型中，并与TNF和NOD样受体信号通路富集有关，表明在肿瘤炎症和进展中的潜在作用。在单细胞层面,间充质样恶性细胞显示高NF，NLR,与其他恶性细胞类型相比，IL-1信号通路富集。
结论：我们揭示了NLRC4炎性体活性与LLT-1表达之间的关联，提示涉及TNF的新调节途径，炎性体,和IL-1，可能提供新的NK细胞介导的抗神经胶质瘤方法。
