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bioRxiv · 10.1101/2022.09.13.507746

Single-cell transcriptomics reveal distinct subsets of activated dendritic cells in the tumor microenvironment

To, T. K. J.·Devalaraja, S.·Folkert, I. W.·Zhai, L.·Lobel, G. P.·Haldar, M.
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Abstract

Dendritic cells (DCs) are rare in tumors where their heterogeneity remains unclear. To overcome the limitations of surface marker-based analyses, we utilized DC-reporter mice (Zbtb46GFP/+) to isolate tissue and tumor DCs and performed single-cell RNA sequencing (scRNA-seq). The known DC subsets were conserved across tissues, albeit at different frequencies. Activated and mature DCs formed a distinct cluster in both healthy and tumor tissues and displayed the hallmark DC migratory program (migratory DCs). We also identified a distinct subset of activated DCs in tumors that did not induce the migratory program, instead displaying signatures of interferon exposure (interferon-DCs or IFN-DCs). IFN-DCs were proficient in antigen-presentation, supported T cell proliferation, and expressed high levels of T cell-attracting chemokines. IFN-DCs further comprised of IFN1- and IFN2-DCs that were generated from CD11b+ DCs in response to type I or type II interferons respectively. We also identified IFN-DCs in scRNA-seq of human tumor-infiltrating leukocytes. These findings illustrate DC heterogeneity in tumors and suggest the existence of an interferon regulated division of labor among activated DCs whereby the migratory DCs drive T cell priming in draining lymph nodes while the sessile IFN-DCs help recruit T cells and regulate their function in the tumor microenvironment. One Sentence SummaryTumors harbor an interferon-regulated activated sessile subset of dendritic cells.

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To, T. K. J., Devalaraja, S., Folkert, I. W., Zhai, L., Lobel, G. P., Haldar, M.. 2022-09-15. Single-cell transcriptomics reveal distinct subsets of activated dendritic cells in the tumor microenvironment. https://doi.org/10.1101/2022.09.13.507746

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