DC subsets and states unraveled across human juxtatumoral and malignant tissues

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells. While plasmacytoid DCs (pDCs) are poor antigen-presenting cells at steady state, myeloid DCs (mDCs), which include DC1s, DC2s and DC3s, are specialized in T cell priming. To generate unbiased human DC atlases, we integrated DCs from 13 tumor tissues across 40 datasets to create a pDC + mDC-VERSE (DC-VERSE) and an mDC-VERSE single-cell RNA-sequencing compendium. We characterized DC subsets and 'states' across these tissues. Most studied tumors contained CD207⁺ DCs, a subset of CD1c⁺ DCs, whose expansion inversely correlated with tumor CD8⁺ resident memory T cells, T cell clonality and the survival of patients treated with immune checkpoint inhibitors. Similarly to CCR7⁺ mDCs (a common state of DC1s, DC2s and DC3s), we found that CD207⁺ DCs were a common state of DC2s and DC3s. Spatially resolved single-cell transcriptomic and immunohistofluorescence analyses of human carcinomas demonstrated that lymphocytes and most DCs were enriched within the tumor stroma, while CD207⁺ DCs were mostly embedded within tumor nests. These DC-VERSEs provide a robust resource available to the scientific community on DCs in health and pathology.