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.
Details
Serval ID
serval:BIB_260FD4BEF65D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of Immunology
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Publication state
Published
Issued date
2000
Volume
165
Number
11
Pages
6278-6286
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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.
Keywords
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, CpG Islands/immunology, Dendritic Cells/cytology, Dendritic Cells/immunology, 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
Pubmed
Create date
26/11/2011 14:06
Last modification date
20/08/2019 14:04