Tro-score, a trogocytosis-related transcriptomic signature, identifies CD109 as a therapeutic target for reversing immunosuppression in bladder cancer.

Trogocytosis, the contact-dependent exchange of membrane fragments between cells, is emerging as a critical regulator of tumor biology, yet its specific role in bladder cancer (BLCA) remains largely unexplored. In this study, we systematically characterized the trogocytosis-associated transcriptional landscape in BLCA and developed a robust prognostic framework, the Tro-score, based on five key genes (CLSTN2, CD109, KANK4, CTSE, and BCAS1). Validated across multiple independent cohorts, a high Tro-score was significantly associated with poor overall survival and a distinct immunosuppressive microenvironment characterized by the enrichment of Tregs, M2 macrophages, and myeloid-derived suppressor cells. Notably, the Tro-score served as a potent predictor of immunotherapy outcomes, with high-score patients exhibiting increased T-cell dysfunction and reduced clinical responsiveness to immune checkpoint inhibitors. Mechanistically, we pinpointed CD109 as a core molecular correlate of this immunosuppressive landscape through integrative analysis. To biologically validate these computational findings, we conducted extensive in vitro and in vivo experiments. Strikingly, in murine models receiving anti-PD-1 therapy and co-culture systems, we demonstrated that CD109 overexpression not only promotes tumor proliferation and invasion but also is associated with inhibited immune cell chemotaxis and CD8+ T-cell cytotoxicity. These findings raise the hypothesis that tumor cells may exploit trogocytosis-related pathways to create a bidirectional interaction network that favors immune evasion-a concept that warrants direct experimental validation in future studies.