DC subsets and states unraveled across human juxtatumoral and malignant tissues.

Nature immunology
Authors
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.

Year of Publication
2025
Journal
Nature immunology
Date Published
12/2025
ISSN
1529-2916
DOI
10.1038/s41590-025-02337-x
PubMed ID
41361070
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