| First Author | Lee CYC | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 682 |
| PubMed ID | 38267413 | Mgi Jnum | J:346024 |
| Mgi Id | MGI:7578340 | Doi | 10.1038/s41467-024-44787-1 |
| Citation | Lee CYC, et al. (2024) Tumour-retained activated CCR7(+) dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity. Nat Commun 15(1):682 |
| abstractText | 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. |
