Stromal reprogramming in urachal cancer: Fibroblast activation protein and collagen remodeling drive immune-suppressive niches and immunotherapy resistance.

Urachal carcinoma is a rare and aggressive malignancy with poor responsiveness to immune checkpoint inhibitors and limited therapeutic options. In this study, we evaluated the expression of fibroblast activation protein (FAP) and collagen deposition in 29 urachal carcinoma specimens using immunohistochemistry and Masson trichrome staining, and assessed their relationship with clinicopathological features and drug response. FAP was universally expressed in cancer-associated fibroblasts (CAFs), with high levels correlating with advanced stage and lymph node metastasis. Collagen fibers were abundant in both intratumoral and peritumoral regions, and PD-L1 positivity was rare (3.4 %). All patients receiving PD-1 inhibitors exhibited disease progression. Patient-derived organoid models demonstrated broad resistance to chemotherapy and targeted agents, consistent with clinical outcomes. Although mechanistic validation was not performed, the spatial co-enrichment of FAP CAFs and collagen supports a stromal-mediated immune exclusion model. These findings highlight the potential of stromal reprogramming strategies as therapeutic targets in urachal carcinoma.