Dendritic cell-mediated antigen presentation regulates tertiary lymphoid structure development in cancer.

Through high-resolution spatial mapping across human tumors, we identified a consistent accumulation of CCR7⁺ mature dendritic cells (DC) within TLS. To dissect their function, we developed a non-small cell lung cancer (NSCLC) model that recapitulates mature TLS formation.

Using this model, we demonstrate that TLS induction requires IFNγ-driven maturation of type 1 conventional dendritic cells (cDC1), their migration to tumor-draining lymph nodes (tdLN), and the subsequent recruitment of tdLN-primed T cells into the tumor microenvironment. As tumors progress, TLS persist even in the absence of tdLN T cell egress, coinciding with impaired cDC1 migration to tdLN and their retention within intratumoral stromal hubs enriched in CCR7 ligands.