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Trends Immunol. 2010 Oct;31(10):391-7. doi: 10.1016/ Epub 2010 Sep 9.

Impaired Toll-like receptor 7 and 9 signaling: from chronic viral infections to cancer.

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INSERM UMR891, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Université Méditerranée, 27 Boulevard Leï Roure, 13273 Marseille, France.


HIV-1, hepatitis B virus, hepatitis C virus, and human papillomavirus type 16 cause persistent infections that frequently precede cancer development. Virions of these viruses are weak inducers of interferon-α and impair Toll-like receptor (TLR)9 function. Loss of TLR9 responsiveness also occurs in tumors without viral etiology such as breast, ovary, and head and neck carcinomas. Recent reports have suggested that viruses and components of the tumor microenviroment interact with regulatory receptors on plasmacytoid dendritic cells (pDCs) to impair TLR7 and TLR9 signaling, and to downregulate TLR9 gene expression. The limited responsiveness of pDCs might contribute to reduced innate immune responses during chronic viral infections and oncogenesis, and represent a target for new therapeutic approaches based on TLR agonists.

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