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 γ, 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.
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19 August 2002
Article|
August 19 2002
Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti–Interleukin 10 Receptor Antibody
Alain P. Vicari,
Alain P. Vicari
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Claudia Chiodoni,
Claudia Chiodoni
2Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
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Céline Vaure,
Céline Vaure
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Smina Aït-Yahia,
Smina Aït-Yahia
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Christophe Dercamp,
Christophe Dercamp
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Fabien Matsos,
Fabien Matsos
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Olivier Reynard,
Olivier Reynard
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Catherine Taverne,
Catherine Taverne
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Philippe Merle,
Philippe Merle
3Institut National de la Sante et de la Recherche Medicale U271, 69424 Lyon, France
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Mario P. Colombo,
Mario P. Colombo
2Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
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Anne O'Garra,
Anne O'Garra
4DNAX Research Institute, Palo Alto, CA 94304
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Giorgio Trinchieri,
Giorgio Trinchieri
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Christophe Caux
Christophe Caux
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
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Alain P. Vicari
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Claudia Chiodoni
2Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
Céline Vaure
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Smina Aït-Yahia
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Christophe Dercamp
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Fabien Matsos
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Olivier Reynard
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Catherine Taverne
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Philippe Merle
3Institut National de la Sante et de la Recherche Medicale U271, 69424 Lyon, France
Mario P. Colombo
2Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy
Anne O'Garra
4DNAX Research Institute, Palo Alto, CA 94304
Giorgio Trinchieri
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Christophe Caux
1Schering-Plough Laboratory for Immunological Research, 69571 Dardilly, France
Address correspondence to Alain P. Vicari, Schering-Plough Laboratory for Immunological Research, BP11, 27 chemin des Peupliers, 69571 Dardilly, France. Phone: 33-4-72-17-27-00; Fax: 33-4-78-35-47-50; E-mail: [email protected]
A. O'Garra's present address is The National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
*
Abbreviations used in this paper: BM-DC, bone marrow–derived DC; DC, dendritic cell; TAA, tumor-associated antigen; TIDC, tumor-infiltrating DC.
Received:
May 06 2002
Revision Received:
July 11 2002
Accepted:
July 17 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (4): 541–549.
Article history
Received:
May 06 2002
Revision Received:
July 11 2002
Accepted:
July 17 2002
Citation
Alain P. Vicari, Claudia Chiodoni, Céline Vaure, Smina Aït-Yahia, Christophe Dercamp, Fabien Matsos, Olivier Reynard, Catherine Taverne, Philippe Merle, Mario P. Colombo, Anne O'Garra, Giorgio Trinchieri, Christophe Caux; Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti–Interleukin 10 Receptor Antibody . J Exp Med 19 August 2002; 196 (4): 541–549. doi: https://doi.org/10.1084/jem.20020732
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