{
  "abstract": "Background Tumour cell uptake and processing by dendritic cells (DC) is the first step in initiating anti-tumour immune responses. Multiple DC subsets exist in human tumours, including conventional DCs (cDC1 and cDC2) and the recently defined ‘mature DC enriched in immunoregulatory molecules’ (mregDC) state. However, the rarity of human DCs limits functional studies, and their contributions to anti-tumour immunity remain unclear. Here, we report the curation of publicly available single-cell RNA sequencing datasets to generate a comprehensive atlas of myeloid antigen-presenting cells (APCs) in human cancer. This atlas represents a powerful resource enabling investigation of tumour-associated DCs in greater detail than previously possible.Methods Single-cell RNA sequencing datasets from 36 studies were analysed individually, and myeloid APCs were extracted and merged into a single atlas. Rigorous batch correction and cleaning were applied to ensure the validity of the resource. Populations were identified using published signatures and canonical markers. The atlas was then used to investigate DC heterogeneity and function across human cancers. Analyses were performed using Seurat (v5.1.0, R v4.3.3) and Scanpy (v1.10.2, Python v3.12.3) pipelines.Results We have curated the largest single-cell representation of human myeloid APCs, comprising 498,023 cells from 589 samples across 12 solid tumour types, including primary and metastatic samples and associated healthy tissue. The atlas contained predominantly tissue-resident macrophages, with smaller populations of monocytes and DCs. We confirmed that cDC1, cDC2, and mregDC represent the major DC subsets present in human tumours. While we aimed to identify cDC2 sub-populations reported in circulation, these were not all discrete in tissue, highlighting cDC2 heterogeneity. Overlaying a previously published in vitro-derived signature of tumour uptake by human cDC1,1 we found this signature aligned with the mregDC state and was conserved across cancer types. This provides evidence that tumour uptake at the tumour site by human cDC1 induces the mregDC phenotype. We have also identified cancer type-specific differences in pathway enrichment across DC subsets. Ongoing work aims to further explore these differences and the maturation of cDCs to mregDC within tumours.Conclusions We present the largest single-cell atlas of human myeloid APCs in cancer, offering a valuable tool for the field. We have confirmed the core DC subsets consistently present in human tumours, provided evidence that tumour uptake induces the mregDC state in human cDC1s, and identified cancer-specific variation in DC phenotype and maturation. Insights from this work will be critical in understanding DC function and informing future DC-based therapies.Reference Belabed M, Park MD, Blouin CM, et al. Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer. Nat Immunol. 2025;26:188-199.Ethics Approval This study utilised previously published and publicly available sequencing data, all studies had appropriate ethics approval for the collection and distribution of the data.",
  "authors": [
    {
      "affiliations": [
        "Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia"
      ],
      "name": "Nikita Rosendahl"
    },
    {
      "affiliations": [
        "Ian Frazer Centre for Children’s Immunotherapy Research, Child Health Research Centre, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, South Brisbane, QLD, Australia"
      ],
      "name": "Xiaohan Xu"
    },
    {
      "affiliations": [
        "Ian Frazer Centre for Children’s Immunotherapy Research, Child Health Research Centre, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, South Brisbane, QLD, Australia"
      ],
      "name": "Norman Teik-Wei Yap"
    },
    {
      "affiliations": [
        "Ian Frazer Centre for Children’s Immunotherapy Research, Child Health Research Centre, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, South Brisbane, QLD, Australia"
      ],
      "name": "Zewen Kelvin Tuong"
    },
    {
      "affiliations": [
        "Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia"
      ],
      "name": "Kristen J Radford"
    }
  ],
  "title": "768 Single-cell atlases of myeloid antigen-presenting cells converge in human cancer",
  "uid": "7917b0e9-835d-50f3-8068-1677b5cb2e3a"
}