The MYC/TXNIP axis mediates NCL-Suppressed CD8⁺T cell immune response in lung adenocarcinoma

Lung adenocarcinoma is a deadly malignancy with immune evasion playing a key role in tumor progression. Glucose metabolism is crucial for T cell function, and the nucleolar protein NCL may influence T cell glucose metabolism. This study aims to investigate NCL's role in T cell glucose metabolism and immune evasion by lung adenocarcinoma cells.

Utilizing single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we analyzed cell clustering, annotation, and prognosis. In vitro experiments involved manipulating NCL expression in CD8⁺ T cells to study immune function and glucose metabolism. In vivo studies using an orthotopic transplant mouse model monitored NCL's impact on CD8⁺ T cell glucose metabolism and anti-tumor immune function.

NCL was associated with T cell dysfunction and glucose metabolism. NCL silencing enhanced CD8⁺ T cell glucose metabolism, cytotoxicity, and infiltration, while NCL overexpression had the opposite effect. NCL overexpression relieved MYC-mediated transcriptional repression of TXNIP, reducing CD8⁺ T cell glucose metabolism. In vivo, NCL inhibited CD8⁺ T cell glucose metabolism through the MYC/TXNIP axis, hindering anti-tumor immune function.

NCL overexpression suppresses CD8⁺ T cell glucose metabolism and anti-tumor immune function, promoting lung adenocarcinoma progression via the MYC/TXNIP axis.