Correlation of LLT-1 and NLRC4 inflammasome and its effect on glioblastoma prognosis

• Published in: Journal of neuro-oncology 2024-09, Vol.169 (3), p.543-553
• Main Authors: Park, JeongMan, Kim, Yu Jin, Lee, Minwook, Kim, Dongkil, Sim, JeongMin, Cho, Kyunggi, Moon, Ju Hyung, Sung, Kyoung Su, Lee, Dong Hyeon, Lim, Jaejoon
• Format: Article
• Language: English
• Subjects: Astrocytes; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; CARD Signaling Adaptor Proteins - genetics; CARD Signaling Adaptor Proteins - metabolism; Female; Glial fibrillary acidic protein; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioma; Glioma cells; Humans; Immunofluorescence; Inflammasomes; Inflammasomes - metabolism; Interleukin 1; Ligands; Male; Malignancy; Medical prognosis; Medical records; Medicine; Medicine & Public Health; Middle Aged; Natural killer cells; Neurology; Oncology; Prognosis; Protein interaction; Proteins; Ribonucleic acid; RNA; Signal transduction; Tumor necrosis factor; Tumors
• ISSN: 0167-594X; 1573-7373; 1573-7373
• DOI: 10.1007/s11060-024-04750-y

Purpose 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. Conclusion 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.