Pan-cancer single-cell atlas of mouse and human tumor-associated dendritic cells reveals diverse dendritic cell subsets and states

Dendritic cells (DCs) are the key orchestrators of anti-tumor immunity. Multiple studies have described several DC subsets/states in inflammation and homeostasis, often using non-consistent nomenclature, complicating the comparison across studies. To bridge this knowledge gap in cancer, we have generated mouse and human tumor-associated DC (TADC) scRNA-seq atlases consisting of 5 mouse and 10 human cancer types.
In both atlases, we identified known DC subsets/states including cDC1, cDC2a, cDC2b, DC3, CCR7+ DCs, and DC precursors along with new DC states that we describe for the first time in cancer. Importantly, the majority of DC subsets were present in both species and shared common gene signatures. To evaluate the influence of tumors on DCs in lymphoid organs, we compared TADCs with DCs from the bone marrow, spleen, and lymph nodes (LN) of naïve and tumor-bearing mice. Interestingly, we identified several tumor-restricted DC states that are absent in the lymphoid organs of tumor-bearing and naïve mice. Furthermore, to evaluate the antigen uptake and presentation capacity of CCR7+ DCs, we identified different stages of CCR7+ DC maturation starting from mature tumor-resident inflammatory DCs to T-cell activating states in the tumor-draining LN. Aiming to assess the mouse-to-human translatability of our data, we highlight the gene and regulon activity correlation between pan-cancer mouse and human TADC subsets/states. Finally, correlations between gene signatures of human TADC subsets/states with disease prognosis were determined, wherein CCR7+ cDC2 subsets predicted the most favorable disease prognosis, while certain states of cDC2b were associated with poor prognosis.
In conclusion, our mouse and human pan-cancer TADC atlases (which will be made publicly available as interactive online tools) serve as valuable resources for characterizing the DC landscape across tumors, tumor-associated, and naive lymphoid organs. A comprehensive understanding of TADCs across different cancers could give insights into potential DC-targeted anti-cancer strategies in the future.