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

CTHRC1-expressing CAFs identify poor-outcome, immunotherapy-resistant colorectal cancers, especially in pMMR/MSS and MSI subtypes, with 3000+ patient samples analyzed.

• Why it matters: Current biomarkers fail to reliably predict treatment response and prognosis in colorectal cancer due to tumor heterogeneity and lack of stromal markers, limiting personalized therapy options.
• What they did: A multiomic approach combining single-cell RNA sequencing, computational deconvolution, and protein analysis was used to identify CTHRC1(+) CAFs associated with poor outcomes and immune resistance across diverse patient cohorts.
• The result: Detection of CTHRC1(+) CAFs enables stratification of CRC into immune-inflamed and poorly immunogenic subtypes, highlighting their potential as routine biomarkers and therapeutic targets, especially for stroma-rich, treatment-resistant tumors.