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Publication : Cell-associated double-stranded RNA enhances antitumor activity through the production of type I IFN.

First Author  McBride S Year  2006
Journal  J Immunol Volume  177
Issue  9 Pages  6122-8
PubMed ID  17056539 Mgi Jnum  J:140522
Mgi Id  MGI:3814023 Doi  10.4049/jimmunol.177.9.6122
Citation  McBride S, et al. (2006) Cell-associated double-stranded RNA enhances antitumor activity through the production of type I IFN. J Immunol 177(9):6122-8
abstractText  The efficacy of tumor cell vaccination largely depends on the maturation and activation status of the dendritic cell. Here we investigated the ability of soluble and tumor cell-associated dsRNA to serve as an adjuvant in the induction of protective adaptive antitumor responses. Our data showed that cell-associated dsRNA, but not soluble dsRNA, enhanced both tumor-specific CD8(+) and CD4(+) T cell responses. The cell-associated dsRNA increased the clonal burst of tumor-specific CD8(+) T cells and endowed them with an enhanced capacity for expansion upon a secondary encounter with tumor Ags, even when the CD8(+) T cells were primed in the absence of CD4(+) T cell help. The adjuvant effect of cell-associated dsRNA was fully dependent on the expression of TLR3 by the APCs and their subsequent production of type I IFNs, as the adjuvant effect of cell-associated dsRNA was completely abrogated in mice deficient in TLR3 or type I IFN signaling. Importantly, treatment with dsRNA-associated tumor cells increased the number of tumor-infiltrating lymphocytes and enhanced the survival of tumor-bearing mice. The data from our studies suggest that using cell-associated dsRNA as a tumor vaccine adjuvant may be a suitable strategy for enhancing vaccine efficacy for tumor cell therapy in cancer patients.
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