MNDA promotes immunosuppression in microsatellite instability-high colorectal cancer by facilitating PMN-MDSC infiltration via H3K18 lactylation.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) have demonstrated significant clinical benefit in colorectal cancer (CRC) with microsatellite instability-high (MSI-H) status, yet a substantial subset of patients remains resistant to therapy. Understanding the mechanisms of resistance and identifying new therapeutic targets are urgently needed.

Methods

We established a murine MC38-based MSI-H CRC model to investigate the variability in PD-1 treatment response and performed single-cell RNA sequencing (scRNA-seq) on tumors from patients with PD-1-sensitive and PD-1-resistant CRC. Immune cell subsets and signaling pathways were analyzed using CellChat and AUCell, and gene expression enrichment was performed. Functional assays, including RNA-seq

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12495719 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature