Positioning and reversible suppression of CCR7(+) dendritic cells in perivascular tumor niches shape cancer immunity.

Tumor-resident CCR7(+) dendritic cells (DCs) are key determinants of antitumor T cell responses. Here, we examined the localization of CCR7(+) DCs within tumors and the impact of this positioning on antitumor immunity. Spatial, single-cell, and intravital analyses of human cancers and mouse models reveal that CCR7(+) DCs form perivascular clusters. Fibroblasts surrounding venous blood vessels produced CCL19, guiding CCR7(+) DCs into perivascular niches. Regulatory T (Treg) cells frequently contact perivascular CCR7(+) DCs, suppressing CD40 expression and CD4(+) and CD8(+) T cell activation. Treg cell depletion restored CD40 expression by CCR7(+) DCs, enhanced immunostimulatory programs, and improved T cell-dependent tumor control. Anti-PD-1 not only increased perivascular CCR7(+) DC clustering and IL-12 production but also strengthened Treg-DC interactions through a CCL22-dependent mechanism, limiting therapeutic efficacy. CCR7(+) DCs expressed both co-stimulatory and co-inhibitory molecules, which may underlie their capacity for antitumor activation and concurrent vulnerability to suppression. Modulating the mechanisms that form and restrain CCR7(+) DC perivascular immune hubs may improve cancer immunotherapy.