2532 Background: Microsatellite-stable (MSS) colorectal cancer (CRC) is typically immune-cold, limiting the routine use of immune checkpoint inhibitors (ICIs). However, a subset of MSS CRC patients may still derive benefit from ICIs. Leveraging an AI-powered whole-slide image (WSI) analyzer applied to hematoxylin and eosin (H P=0.026; median OS, 11.6 vs. 6.6 months; P=0.024). High endothelial cell and fibroblast densities within the CA were not significantly associated with PFS (P=0.160, P=0.112, respectively), but were associated with worse OS, with a significant association for endothelial cells (median, 7.6 vs. 14.7 months; P=0.024) and a trend toward worse OS for fibroblasts (median, 8.9 vs. 12.2 months; P=0.056). Higher macrophage density within the CA showed a favorable trend toward improved PFS (median, 10.2 vs. 8.5 months, P=0.092), but was not associated with OS (P=0.399). In contrast, none of these biomarkers were associated with clinical outcomes in the first-line chemotherapy. Conclusions: Despite microsatellite-stable status, a higher summed TLS area was associated with improved progression-free and overall survival following immunotherapy, with endothelial cell and fibroblast densities providing additional prognostic information. AI-powered WSI analysis enabled effective stratification of these features.
Kim et al. (2026) studied this question.