Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody

Progressing tumors in man and mouse are often infiltrated by dendritic cells (DCs). Deficient antitumor immunity could be related to a lack of tumor-associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a functional defect of TIDCs. Here we investigated the phenotype and func...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2002-08, Vol.196 (4), p.541-549
Main Authors: Vicari, Alain P, Chiodoni, Claudia, Vaure, Céline, Aït-Yahia, Smina, Dercamp, Christophe, Matsos, Fabien, Reynard, Olivier, Taverne, Catherine, Merle, Philippe, Colombo, Mario P, O'Garra, Anne, Trinchieri, Giorgio, Caux, Christophe
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Animals
Antibodies, Monoclonal - immunology
Antigens, Tumor-Associated, Carbohydrate - immunology
CD40 Antigens - immunology
CD8-Positive T-Lymphocytes - immunology
CpG Islands - immunology
Dendritic Cells - cytology
Dendritic Cells - immunology
Female
Immunity, Active - immunology
Immunity, Innate - immunology
Immunologic Memory - immunology
Interferon-gamma - immunology
Interferon-gamma - pharmacology
Killer Cells, Natural - immunology
Lipopolysaccharides - immunology
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, SCID
Oligodeoxyribonucleotides - immunology
Oligodeoxyribonucleotides - pharmacology
Receptors, Interleukin - immunology
Receptors, Interleukin-10
Tumor Cells, Cultured
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Progressing tumors in man and mouse are often infiltrated by dendritic cells (DCs). Deficient antitumor immunity could be related to a lack of tumor-associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a functional defect of TIDCs. Here we investigated the phenotype and function of TIDCs in transplantable and transgenic mouse tumor models. Although TIDCs could encompass various known DC subsets, most had an immature phenotype. We observed that TIDCs were able to present TAA in the context of major histocompatibility complex class I but that they were refractory to stimulation with the combination of lipopolysaccharide, interferon gamma, and anti-CD40 antibody. We could revert TIDC paralysis, however, by in vitro or in vivo stimulation with the combination of a CpG immunostimulatory sequence and an anti-interleukin 10 receptor (IL-10R) antibody. CpG or anti-IL-10R alone were inactive in TIDCs, whereas CpG triggered activation in normal DCs. In particular, CpG plus anti-IL-10R enhanced the TAA-specific immune response and triggered de novo IL-12 production. Subsequently, CpG plus anti-IL-10R treatment showed robust antitumor therapeutic activity exceeding by far that of CpG alone, and elicited antitumor immune memory.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20020732