Marginating Dendritic Cells of the Tumor Microenvironment Cross-Present Tumor Antigens and Stably Engage Tumor-Specific T Cells

Engelhardt, J. J., Boldajipour, B., Beemiller, P., Pandurangi, P., Sorensen, C., Werb, Z., Egeblad, M., Krummel, M. F (2012) Marginating Dendritic Cells of the Tumor Microenvironment Cross-Present Tumor Antigens and Stably Engage Tumor-Specific T Cells. Cancer Cell, 21 (3). pp. 402-417. ISSN 1535-6108

Abstract

Summary 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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
CSHL Authors:	Egeblad, Mikala
Communities:	CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL labs > Egeblad lab CSHL Cancer Center Program > Signal Transduction
Depositing User:	Matt Covey
Date:	2012
Date Deposited:	31 Jan 2013 19:44
Last Modified:	15 Oct 2015 20:06
PMCID:	PMC3311997
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26935

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