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

## TL;DR

This study shows that NCL suppresses CD8+ T cell function in lung adenocarcinoma by affecting glucose metabolism through the MYC/TXNIP pathway.

## Contribution

The study identifies the MYC/TXNIP axis as a novel mechanism by which NCL regulates T cell metabolism and immune evasion in lung cancer.

## Key findings

- NCL overexpression reduces CD8+ T cell glucose metabolism and cytotoxicity.
- NCL silencing enhances T cell infiltration and anti-tumor immune function.
- NCL promotes tumor progression by inhibiting T cell metabolism via the MYC/TXNIP axis.

## Abstract

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.

The online version contains supplementary material available at 10.1186/s10020-025-01224-3.