Tumor-Associated Dendritic Cell Sub-Populations in Cancer Immunity
Jo A. Van Ginderachter1,2 1 Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium; 2 Cellular and Molecular Immunology Lab, Vrije Universiteit Brussel, Brussels, Belgium
Various steady-state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1, cDC2 and monocyte-derived DC, displaying differential functional specializations. The identification of functionally distinct tumor-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrated that multiple mouseas well as human tumorsharbor ontogenically discrete TADC subsets. Monocyte-derived TADC are prominent in tumor antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADC have lymph node migratory potential, whereby cDC1 efficiently activate CD8+ T cells and cDC2 induce Th17 cells. Evidence will be presented that tumor-derived cDC1 and cDC2 induce immunity to different tumor types. These data may prove important for therapeutic interventions targeted at specific TADC subsets or their precursors.
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