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Cancer Immunology, Immunotherapy

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01-04-2009 | Original Article

Interferon regulatory factor 8 mediates tumor-induced inhibition of antigen processing and presentation by dendritic cells

Authors: Irina L. Tourkova, Galina V. Shurin, Soldano Ferrone, Michael R. Shurin

Published in: Cancer Immunology, Immunotherapy | Issue 4/2009

Abstract

Introduction

Suppression of dendritic cells (DCs) is a crucial mechanism by which tumor cells escape immune recognition and elimination. We have recently reported that MHC class I antigen processing machinery (APM) component expression in human DCs is down-regulated by tumor-derived gangliosides. However, the molecular mechanisms underlying this abnormality were not identified. Thus, the aim of this work was to analyze the role of interferon regulatory factor 8 (IRF-8) in APM protein expression and the antigen presenting capacity of DCs developed in the tumor microenvironment.

Results

We demonstrate that the expression of several MHC class I APM components, including delta, MB-1, LMP-10, ERp57, and tapasin, is significantly decreased in murine DCs generated in the presence of prostate cancer cells. APM component down-regulation was associated with decreased ability of DCs to present model antigen to antigen-specific T cells. Notable, impaired antigen-presenting activity of DCs co-cultured with tumor cells was accompanied by decreased levels of IRF-8. Transduction of DCs with the silencing RNA for the IRF-8 gene also led to reduced expression of APM components in DCs and decreased antigen presenting function.

Conclusion

Together, our data suggest that tumor-induced inhibition of antigen processing and presenting function of DCs is mediated by IRF-8, a member of the interferon regulatory factor family. These results provide a new molecular target for optimizing the generation of efficient DC vaccines for cancer therapy.

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Title: Interferon regulatory factor 8 mediates tumor-induced inhibition of antigen processing and presentation by dendritic cells
Authors: Irina L. Tourkova
Galina V. Shurin
Soldano Ferrone
Michael R. Shurin
Publication date: 01-04-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 4/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0579-1

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