Dendritic cells pulsed with leukemia cell-derived exosomes more efficiently induce antileukemic immunities

PLoS One. 2014 Mar 12;9(3):e91463. doi: 10.1371/journal.pone.0091463. eCollection 2014.

Abstract

Dendritic cells (DCs) and tumor cell-derived exosomes have been used to develop antitumor vaccines. However, the biological properties and antileukemic effects of leukemia cell-derived exosomes (LEXs) are not well described. In this study, the biological properties and induction of antileukemic immunity of LEXs were investigated using transmission electron microscopy, western blot analysis, cytotoxicity assays, and animal studies. Similar to other tumor cells, leukemia cells release exosomes. Exosomes derived from K562 leukemia cells (LEXK562) are membrane-bound vesicles with diameters of approximately 50-100 μm and harbor adhesion molecules (e.g., intercellular adhesion molecule-1) and immunologically associated molecules (e.g., heat shock protein 70). In cytotoxicity assays and animal studies, LEXs-pulsed DCs induced an antileukemic cytotoxic T-lymphocyte immune response and antileukemic immunity more effectively than did LEXs and non-pulsed DCs (P<0.05). Therefore, LEXs may harbor antigens and immunological molecules associated with leukemia cells. As such, LEX-based vaccines may be a promising strategy for prolonging disease-free survival in patients with leukemia after chemotherapy or hematopoietic stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / ultrastructure
  • Exosomes / pathology*
  • Female
  • Humans
  • K562 Cells
  • Leukemia / immunology*
  • Leukemia / pathology*
  • Mice
  • Microscopy, Electron, Transmission
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology

Grants and funding

This research was supported by the National Natural Science Foundation of China (grant No. 81070432). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.