24 January 2024 | Colin Y. C. Lee, Bethany C. Kennedy, Nathan Richoz, Isaac Dean, Zewen K. Tuong, Fabrina Gaspal, Zhi Li, Claire Willis, Tetsuo Hasegawa, Sarah K. Whiteside, David A. Posner, Gianluca Carlesso, Scott A. Hammond, Simon J. Dovedi, Rahul Roychoudhuri, David R. Withers, Menna R. Clatworthy
This study investigates the spatio-temporal dynamics and functional roles of tumor-retained activated CCR7+ dendritic cells (DCs) in anti-tumor immune responses. Using a photo-tracking mouse model, the researchers found that while CCR7+ DCs are the dominant population migrating to draining lymph nodes (dLNs), a subset remains tumor-resident despite CCR7 expression. These tumor-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and exhibit a "exhausted" state with prolonged tumor residence. They downregulate antigen presentation and pro-inflammatory transcripts, but co-localize with PD-1+CD8+ T cells in human and murine solid tumors. Following anti-PD-L1 treatment, tumor-retained CCR7+ DCs upregulate stimulatory molecules like XO40L, enhancing anti-tumor cytolytic activity. The study highlights the previously unappreciated heterogeneity of CCR7+ DCs and their role in supporting intratumoral cytotoxic T cells, which may influence the effectiveness of cancer immunotherapy.This study investigates the spatio-temporal dynamics and functional roles of tumor-retained activated CCR7+ dendritic cells (DCs) in anti-tumor immune responses. Using a photo-tracking mouse model, the researchers found that while CCR7+ DCs are the dominant population migrating to draining lymph nodes (dLNs), a subset remains tumor-resident despite CCR7 expression. These tumor-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and exhibit a "exhausted" state with prolonged tumor residence. They downregulate antigen presentation and pro-inflammatory transcripts, but co-localize with PD-1+CD8+ T cells in human and murine solid tumors. Following anti-PD-L1 treatment, tumor-retained CCR7+ DCs upregulate stimulatory molecules like XO40L, enhancing anti-tumor cytolytic activity. The study highlights the previously unappreciated heterogeneity of CCR7+ DCs and their role in supporting intratumoral cytotoxic T cells, which may influence the effectiveness of cancer immunotherapy.