Cross-tissue single-cell meta-analysis of human tumor-infiltrating dendritic cells​

Dendritic cells (DC), despite being a rare population, are crucial players in coordinating the antigen-specific immunity response to various insults, including cancer. Based on their ontogeny and phenotype, DCs are subdivided into plasmacytoid (pDCs); two conventional (cDC) types - cDC1/DC1 and cDC2/DC2; CCR7+ migratory DCs (migDCs, also referred to as mregDCs, LAMP3+ DCs or DC3), DCs combining the profile of cDCs and monocytes (DC3); and monocyte-derived DCs (mo-DC). Multiple studies have described the presence of DCs in tumors, however often using non-consistent nomenclature for cDC subtypes, complicating the comparison between studies. ​
Aiming to bridge this knowledge gap, we integrated mononuclear phagocytes (MNP) from 10 different tumor single-cell sequencing (scRNAseq) datasets, resulting in an atlas of 66 056 cells, allowing us to fine-map the MNP tumor microenvironment and identify conserved gene expression signatures across tumor types. Next, we focused our analysis on the DCs, encompassing a total of 10 693 cells and including pDCs, cDC1, cDC2, migDCs and DC precursors. The cDC2 cells were classified into 11 clusters, including previously characterized cDC2A, cDC2B, DC3 and DC precursors, as well as potential novel subtypes.