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<p>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<sup>+</sup> DCs, a subset of CD1c<sup>+</sup> DCs, whose expansion inversely correlated with tumor CD8<sup>+</sup> resident memory T cells, T cell clonality and the survival of patients treated with immune checkpoint inhibitors. Similarly to CCR7<sup>+</sup> mDCs (a common state of DC1s, DC2s and DC3s), we found that CD207<sup>+</sup> 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<sup>+</sup> 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.</p>

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DC subsets and states unraveled across human juxtatumoral and malignant tissues

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • Kevin Mulder,
  • Margaux Gardet,
  • Wan Ting Kong,
  • Amit Ashok Patel,
  • Anne Calvez,
  • Grégoire Gessain,
  • Carlos de la Calle-Fabregat,
  • Cécile Piot,
  • Quentin Blampey,
  • Elisa Poupaud,
  • Ahmed-Amine Anzali,
  • Garett Dunsmore,
  • Antoine Bougouin,
  • Guilhem Pupier,
  • Lizhi He,
  • Timothy Wiggins,
  • Jiang He,
  • George Emanuel,
  • Anne-Gaëlle Goubet,
  • Ghamdan Al-Eryani,
  • Alexander Swarbrick,
  • Judith Michels,
  • Regine J. Dress,
  • Marc Deloger,
  • Antonio Bertoletti,
  • Vincent Thomas de Montpreville,
  • Catherine Sautès-Fridman,
  • Wolf H. Fridman,
  • Laurence Zitvogel,
  • Florent Ginhoux,
  • Charles-Antoine Dutertre

摘要

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.