Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma

J Neurooncol. 2011 Sep;104(3):659-67. doi: 10.1007/s11060-011-0537-1. Epub 2011 Feb 19.

Abstract

In this study, we demonstrate that tumor-derived exosome-loaded dendritic cells can elicit a specific CD8(+) cytotoxic T-lymphocyte (CTL) response against autologous tumor cells in patients with malignant glioma. Exosomes were purified by ultrafiltration centrifugation and sucrose gradient ultracentrifugation. Exosomes had antigen-presenting molecules (MHC-I, HSP70), tumor antigen (MAGE-1) and adherent molecule (ICAM-1). After incubation with exosomes, the dendritic cells (DCs) could activate the T lymphocytes to become glioma-specialized CTL. The CTL had vigorous cytotoxicity to glioma cells as opposed to autologous lymphoblast cells. These data demonstrate that tumor exosome-loaded DC can be an effective tool in inducing glioma-specific CD8(+) CTLs able to kill autologous glioma cells in vitro. In conclusion, exosomes are a natural and new source of tumor-rejection antigens, opening up new avenues for immunization against glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Chromium / pharmacokinetics
  • Dendritic Cells / physiology*
  • Exosomes / pathology*
  • Exosomes / ultrastructure
  • Female
  • Flow Cytometry
  • Glioblastoma / immunology
  • Glioblastoma / pathology*
  • HSP72 Heat-Shock Proteins / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / physiology*

Substances

  • Antigens, CD
  • HSP72 Heat-Shock Proteins
  • Histocompatibility Antigens Class I
  • Chromium