Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte- macrophage colony-stimulating factor gene-modified tumor cells

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Item Type:	Article
Title:	Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte- macrophage colony-stimulating factor gene-modified tumor cells
Creators Name:	Qin, Z., Noffz, G., Mohaupt, M. and Blankenstein, T.
Abstract:	A wide variety of human tumors express IL-10 for reasons poorly understood. We have analyzed the effect of spontaneous IL-10 expression by a mouse tumor (J558L) on its immunoparalyzing effect. Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells. GM-CSF-secreting cells were not effective when used for immunization against challenge with the parental tumor. Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response. Since the tumor used for challenge produced IL-10, we conclude that IL-10 interfered primarily with the initiation but not the effector phase of the immune response. Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10. In the presence of IL-10, DC accumulation was completely inhibited. Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
Keywords:	Cancer Vaccines, Cultured Tumor Cells, Dendritic Cells, Experimental Neoplasms, Granulocyte-Macrophage Colony-Stimulating Factor, Immunologic Cytotoxicity, Interleukin-10, Neoplastic Gene Expression Regulation, Plasmacytoma, Vaccination, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	159
Number:	2
Page Range:	770-776
Date:	15 July 1997
Official Publication:	http://www.jimmunol.org/cgi/content/abstract/159/2/770
PubMed:	View item in PubMed

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