%0 Journal Article
%T Poly-I:C Decreases Dendritic Cell Viability Independent of PKR Activation
%A Hjalte List Larsen
%A Anders Elm Pedersen
%J Journal of Immune Based Therapies, Vaccines and Antimicrobials
%P 1-6
%@ 2168-1554
%D 2012
%I Scientific Research Publishing
%R 10.4236/jibtva.2012.11001
%X Vaccination with tumor-antigen pulsed, monocyte-derived dendritic cells (DCs) has emerged as a promising strategy in cancer immunotherapy. The standard DC maturation cocktail consists of a combination of tumor necrosis factor-¦Á (TNF-¦Á)/interleukin (IL)-1¦Â/IL-6 and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) for generation of standard DCs (sDCs). In order to improve IL-12p70 production and cytotoxic T-lymphocyte (CTL) induction, a novel cocktail composed of TNF-¦Á/IL-1¦Â/ interferon (IFN)-¦Á/IFN-¦Ã and polyinosinic:polycytidylic acid (Poly-I:C) has been introduced to generate so-called ¦Á-Type-1 polarized DCs (¦ÁDC1s). We and others have previously performed a comprehensive comparison of sDCs and ¦ÁDC1s. Here we demonstrate that the viability of ¦ÁDC1s is lowered compared to sDCs and that DC apoptosis is mediated by Poly-I:C. We speculated that activation of protein kinase R (PKR) could mediate the observed apoptosis, but despite significantly higher PKR expression in ¦ÁDC1s compared to sDCs and induction of active threonine (Thr)446 autophosphorylation of PKR in ¦ÁDC1s, Poly-I:C did not influence total PKR expression or autophosporylation, indicating PKR-independent Poly-I:C-induced DC apoptosis.
%K Cancer Immunotherapy
%K Dendritic Cells
%K Poly-I:C
%K PKR
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=18687