NECTIN4 defines a subtype-dependent tumor state coupling enfortumab vedotin targetability to antitumor immunity in bladder cancer
NECTIN4, the target of enfortumab vedotin (EV), acts as a subtype-dependent determinant of tumor state and antitumor immunity in bladder cancer. Integrating clinical multi-omics, spatial and single-cell immune profiling, and experimental models, the work shows NECTIN4-high basal/squamous muscle-invasive tumors had favorable survival, higher checkpoint inhibitor response rates, and a CD8+ T cell-inflamed microenvironment, with no comparable associations in luminal papillary tumors; NECTIN4-low models were preferentially sensitive to HDAC inhibition.
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