Spatial Organisation of Tumour cDC1 States Correlates with Effector and Stem-Like CD8+ T Cells Location

Abstract

CD8⁺ T cells are central to targeting and eliminating cancer cells. Their function is critically supported by type 1 conventional dendritic cells (cDC1s), which both prime antigen-specific CD8⁺ T cells in tumour-draining lymph nodes (tdLNs) and sustain primed CD8⁺ T cells within tumours. Despite their importance, the spatiotemporal organisation of cDC1s within tumours and their diverse functional roles remain poorly understood. Here, we use scRNAseq and unbiased spatial analysis to construct a detailed map of cDC1 states and distribution within immunogenic mouse tumours during CD8⁺ T-cell-mediated rejection. We reveal two distinct cDC1 activation states characterised by differential expression of genes linked to anti-tumour immunity, including Cxcl9 and Il12b. Strikingly, Il12b-expressing cDC1s are CCR7⁺ and enriched at tumour borders, where they closely associate with stem-like TCF1⁺ CD8⁺ T cells. In contrast, CCR7^– Cxcl9-expressing cDC1s are preferentially found within the tumour parenchyma alongside effector CD8⁺ T cells. Analysis of a published dataset of human tumours similarly reveals a spatial association between CCR7⁺ cDC1 and stem-like TCF1⁺ CD8⁺ T cells. These findings uncover a highly spatially coordinated interaction between cDC1s and CD8⁺ T cells within tumours, shedding light on the intricate cellular dynamics that underpin effective anti-tumour immunity.