Membrane transfer from tumor cells overcomes deficient phagocytic ability of plasmacytoid dendritic cells for the acquisition and presentation of tumor antigens

J Immunol. 2014 Jan 15;192(2):824-32. doi: 10.4049/jimmunol.1301039. Epub 2013 Dec 11.

Abstract

The potential contribution of plasmacytoid dendritic cells (pDCs) in the presentation of tumor cell Ags remains unclear, and some controversies exist with regard to the ability of pDCs to phagocytose cell-derived particulate Ags and cross-present them to MHC class I-restricted T lymphocytes. In this study, we show that human pDCs, although inefficient in the internalization of cell membrane fragments by phagocytosis, can efficiently acquire membrane patches and associated molecules from cancer cells of different histotypes. The transfer of membrane patches to pDCs occurred in a very short time and required cell-to-cell contact. Membrane transfer also included intact HLA complexes, and the acquired Ags could be efficiently recognized on pDCs by tumor-specific CD8(+) T cells. Remarkably, pDCs isolated from human colon cancer tissues displayed a strong surface expression of epithelial cell adhesion molecule, indicating that the exchange of exogenous Ags between pDCs and tumor cells also can occur in vivo. These data demonstrate that pDCs are well suited to acquire membrane patches from contiguous tumor cells by a cell-to-cell contact-dependent mechanism that closely resembles "trogocytosis." This phenomenon may allow pDCs to proficiently present tumor cell-derived Ags, despite limited properties of endophagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Caco-2 Cells
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / immunology*
  • Cell Membrane / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-3 / immunology
  • Interleukin-3 / metabolism
  • K562 Cells
  • MCF-7 Cells
  • Major Histocompatibility Complex / immunology
  • Phagocytosis / immunology*
  • U937 Cells

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • IL3 protein, human
  • Interleukin-3