title: Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells.
abstract: The nature and site of tumor-antigen presentation to immune T cells by bone-marrow-derived cells within the tumor microenvironment remains unresolved. We generated a fluorescent mouse model of spontaneous immunoevasive breast cancer and identified a subset of myeloid cells with significant similarity to dendritic cells and macrophages that constitutively ingest tumor-derived proteins and present processed tumor antigens to reactive T cells. Using intravital live imaging, we determined that infiltrating tumor-specific T cells engage in long-lived interactions with these cells, proximal to the tumor. In vitro, these cells capture cytotoxic T cells in signaling-competent conjugates but do not support full activation or sustain cytolysis. The spatiotemporal dynamics revealed here implicate nonproductive interactions between T cells and antigen-presenting cells on the tumor margin.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Engelhardt
authors.forename: Bijan
authors.initials: B
authors.lastname: Boldajipour
authors.forename: Peter
authors.initials: P
authors.lastname: Beemiller
authors.forename: Priya
authors.initials: P
authors.lastname: Pandurangi
authors.forename: Caitlin
authors.initials: C
authors.lastname: Sorensen
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Mikala
authors.initials: M
authors.lastname: Egeblad
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm