Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells

Cancer Cell. 2012 Mar 20;21(3):402-17. doi: 10.1016/j.ccr.2012.01.008.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cross-Priming*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Lymphocyte Activation
  • Mice
  • Myeloid Cells / immunology
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment*

Substances

  • Antigens, Neoplasm