Spatial microbiome-metabolic crosstalk drives CD8⁺ T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.

ABSTRACT:

Background

The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.

Methods

We integrated single-cell RNA-seq, spatial transcriptomics, and microbial multi-omics from a discovery cohort of 23 treatment-naïve CRC patients. Findings were validated in an independent validation cohort from The Cancer Genome Atlas (TCGA-CRC, n = 159).

Results

Spatial depletion of Streptococcus and Acetivibrio in tumor niches disrupts butyrate-histone deacetylase (HDAC) signaling, leading to programmed cell death 1 (PDCD1) hyperacetylation and CD8⁺ T-cell exhaustion. The Colorectal Cancer Microbiome Score (CMS) may serve as a predictive biomar

SUBMITTER: Chen X 

PROVIDER: S-EPMC12719255 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature