Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with malignant glioma

Cancer Immunol Immunother. 2003 Oct;52(10):632-7. doi: 10.1007/s00262-003-0408-5. Epub 2003 Jun 21.

Abstract

In this study, we demonstrate that tumor mRNA-loaded dendritic cells can elicit a specific CD8(+) cytotoxic T-lymphocyte (CTL) response against autologous tumor cells in patients with malignant glioma. CTLs from three patients expressed strong cytolytic activity against autologous glioma cells, did not lyse autologous lymphoblasts or EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Also, DCs-pulsed normal brain mRNA failed to induce cytolytic activity against autologous glioma cells, suggesting the lack of autoimmune response. Two patients' CD8(+) T cells expressed a modest cytotoxicity against autologous glioma cells. CD8(+) T cells isolated during these ineffective primings secreted large amounts of IL-10 and smaller amounts of IFN-gamma as detected by ELISA. Type 2 bias in the CD8(+) T-cell response accounts for the lack of cytotoxic effector function from these patients. Cytotoxicity against autologous glioma cells could be significantly inhibited by anti-HLA class I antibody. These data demonstrate that tumor mRNA-loaded DC can be an effective tool in inducing glioma-specific CD8(+) CTLs able to kill autologous glioma cells in vitro. However, high levels of tumor-specific tolerance in some patients may account for a significant barrier to therapeutic vaccination. These results may have important implications for the treatment of malignant glioma patients with immunotherapy. DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of glioma antigens.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Transformed
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glioma / genetics
  • Glioma / immunology*
  • Green Fluorescent Proteins
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunophenotyping
  • Luminescent Proteins / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Histocompatibility Antigens Class I
  • Luminescent Proteins
  • RNA, Messenger
  • Green Fluorescent Proteins