Article citationsMore>>
I. J. de Vries, W. J. Lesterhuis, N. M. Scharenborg, L. P. Engelen, D. J. Ruiter, M. J. Gerritsen, et al., “Maturation of Dendritic Cells Is a Prerequisite for Inducing Immune Responses in Advanced Melanoma Patients,” Clinical Cance Research, Vol. 9, 2003, p. 5091.
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TITLE:
Poly-I:C Decreases Dendritic Cell Viability Independent of PKR Activation
AUTHORS:
Hjalte List Larsen, Anders Elm Pedersen
KEYWORDS:
Cancer Immunotherapy; Dendritic Cells; Poly-I:C; PKR
JOURNAL NAME:
Journal of Immune Based Therapies, Vaccines and Antimicrobials,
Vol.1 No.1,
April
25,
2012
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.