Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy.

CTHRC1-expressing CAFs are linked to poor outcomes and immune resistance in both pMMR/MSS and dMMR/MSI colorectal cancers.

• Why it matters: Identifying reliable stromal biomarkers is crucial for improving patient stratification and predicting therapeutic responses in colorectal cancer, where tumor heterogeneity hampers progress.
• What they did: The study used a multiomic approach, including single-cell RNA sequencing and protein assessment, analyzing over 3000 patient samples to identify CTHRC1(+) CAFs associated with TGF-beta signaling and treatment resistance.
• The result: CTHRC1(+) CAFs enable stratification of tumors into immune-inflamed and poorly immunogenic subtypes and are linked to resistance to immune checkpoint inhibitors, suggesting potential for combined TGF-beta blockade and immunotherapy.