CD44-CD206 axis drives dendritic cell loss and immunosuppression in immaturely glycosylated bladder tumours

Immature O-glycosylated bladder tumours linked to Tn and sialyl-Tn drive conventional dendritic cell loss and immunosuppression via a CD44–CD206 axis.

• Why it matters: Antigen-presenting-cell dysfunction contributes to immune exclusion, but the mechanism by which tumour glycans disable these cells is incompletely defined.
• What they did: Transcriptomics and human tumour profiling associated immature O-glycosylation with reduced antigen-presenting myeloid representation and attenuated lymphoid-effector programmes; glycoengineered models showed CD206-bound immature CD44 and CD206 blockade restored moDC viability.
• The result: In immunocompetent mice, immature glycosylation accelerated tumour growth and depleted conventional DCs, while CD206 blockade restrained progression and restored local and nodal myeloid and lymphoid immunity.