Stage-spanning single-cell mapping reveals a T1 vascular–immune barrier linked to BCG response in bladder cancer

T1-stage bladder cancer represents a critical transition in disease progression and BCG responsiveness, yet its microenvironmental basis remains poorly defined. We constructed a stage-spanning single-cell atlas of human bladder cancer and integrated tissue validation with an orthotopic rat model. We identify T1 as a vascular–immune transition state characterized by expansion of CXCR4⁺ tip endothelial cells, metabolically activated pericytes, and SPP1-associated macrophages. CXCR4⁺ endothelium showed strong angiogenic activity but low adhesion molecule expression, forming a vascularly restrictive niche associated with reduced T-cell access and supported by VEGF signals from hypoxia-associated MT1X⁺ macrophages. Concurrently, CXCL13⁺ T cells and TLS-associated B-cell programs emerged at T1, but mature TLSs were preferentially enriched in BCG responders, whereas CXCR4⁺ tip endothelial cells were enriched in non-responders. Pharmacologic targeting of VEGFR/PDGFR signaling with sunitinib enhanced BCG efficacy in vivo. Together, this atlas defines a T1-stage vascular–immunosuppressive niche linking vascular remodeling, immune accessibility, TLS maturation, and BCG responsiveness, providing a mechanistic basis for overcoming BCG resistance.