Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo

J Immunol. 2000 Dec 1;165(11):6278-86. doi: 10.4049/jimmunol.165.11.6278.


Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in experimental murine tumor models. To improve DC-based tumor vaccination, we studied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-alpha or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotide (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA. Flow cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-alpha had an intermediate effect. The extent of maturation correlated with the secretion of IL-12 and the induction of alloreactive T cell proliferation. In BALB/c mice, s.c. injection of colon carcinoma cells resulted in rapidly growing tumors. In this model, CpG-ODN-stimulated DC cocultured with irradiated tumor cells also induced prophylactic protection most effectively and were therapeutically effective when administered 3 days after tumor challenge. Thus, CpG-ODN-enhanced DC maturation may represent an efficient means to improve clinical tumor vaccination.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antineoplastic Agents / immunology*
  • Antineoplastic Agents / therapeutic use
  • Cell Communication / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • CpG Islands / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Female
  • Growth Inhibitors / immunology
  • Growth Inhibitors / therapeutic use
  • Immunotherapy, Adoptive / methods
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Oligodeoxyribonucleotides / immunology*
  • Oligodeoxyribonucleotides / therapeutic use
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured / immunology
  • Tumor Cells, Cultured / transplantation
  • Tumor Necrosis Factor-alpha / immunology*


  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • CPG-oligonucleotide
  • Growth Inhibitors
  • Oligodeoxyribonucleotides
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interleukin-4