Tumour-retained activated CCR7 + dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity.
Colin Y C LeeBethany C KennedyNathan RichozIsaac DeanZewen K TuongFabrina GaspalZhi LiClaire WillisTetsuo HasegawaSarah K WhitesideDavid A PosnerGianluca CarlessoScott A HammondSimon J DovediRahul RoychoudhuriDavid R WithersMenna R ClatworthyPublished in: Nature communications (2024)
Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7 + DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7 + DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7 + DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7 + DCs co-localise with PD-1 + CD8 + T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7 + DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.
Keyphrases
- dendritic cells
- regulatory t cells
- immune response
- poor prognosis
- lymph node
- machine learning
- endothelial cells
- type diabetes
- early stage
- single cell
- binding protein
- long non coding rna
- patient safety
- study protocol
- quality improvement
- deep learning
- case report
- neoadjuvant chemotherapy
- data analysis
- artificial intelligence
- double blind