Poly-I:C Decreases Dendritic Cell Viability Independent of PKR Activation
- 1 University of Copenhagen
Abstract
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-α (TNF-α)/interleukin (IL)-1β/IL-6 and prostaglandin E2 (PGE2) 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-α/IL-1β/ interferon (IFN)-α/IFN-γ and polyinosinic:polycytidylic acid (Poly-I:C) has been introduced to generate so-called α-Type-1 polarized DCs (αDC1s). We and others have previously performed a comprehensive comparison of sDCs and αDC1s. Here we demonstrate that the viability of αDC1s 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 αDC1s compared to sDCs and induction of active threonine (Thr)446 autophosphorylation of PKR in αDC1s, Poly-I:C did not influence total PKR expression or autophosporylation, indicating PKR-independent Poly-I:C-induced DC apoptosis.
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