Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation

Abstract

Dendritic cells (DCs) have the ability to generate peptide epitopes for MHC class I molecules derived from apoptotic tumour cells for direct recognition by cytotoxic T cells. This function has lead to DCs being used in vaccine strategies. In this study, we investigate the effect of inducing apoptosis in tumour cell lines using IFN-γ and poly(I:C), the subsequent maturation of the endocytosing DC and its ability to direct the resulting T cell response. We show that uptake of poly(I:C)-induced apoptotic tumour cells leads to DC maturation and activation with a Th1 cell polarising capacity. In contrast, these effects are not seen by DCs loaded with γ-irradiated apoptotic tumour cells. We propose that the manner in which tumour cells are induced to die can have a profound effect on the endocytosing DC and the resulting T cell response.

Poly(I:C) as cancer vaccine adjuvant: Knocking on the door of medical breakthroughs

“…Although Frleta and colleagues reported an inhibitory effect of poly(I:C) on cross-presentation by human DC in vitro (Frleta et al, 2009), different mouse models showed that poly(I:C) activates DC and stimulates cross-priming in vivo (Datta et al, 2003;Durand, Wong, Tough, & Le Bon, 2006;McBride, Hoebe, Georgel, & Janssen, 2006;Schulz et al, 2005). Furthermore, uptake of poly(I:C)-induced apoptotic tumor cells by human DC results in poly(I:C)-dependent DC maturation, secretion of pro-inflammatory cytokines and an increase in their T helper 1-polarizing capacity in vitro (Kovalcsik, Lowe, Fischer, Dalgleish, & Bodman-Smith, 2011;Smits et al, 2007), which is in favor of efficient anti-tumor immunity. In addition to CTL, NK cells are increasingly being recognized as immune cells with an important role in anti-tumor immunity.…”

RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1α release, and efficient paracrine dendritic cell activation

“…A striking finding of our study was that PolyIC-mediated IL-1α release from cervical cancer cells is required in order to enhance IL-12 production by DC. Given the results of other studies involving PolyIC-treated normal keratinocytes and different cancer types, one would expect that IFNβ and/or TNFα are needed for DC activation [ 20 , 22 , 46 ]. However, we were unable to detect the release of these cytokines in supernatant from cervical cancer cells after PolyIC stimulation.…”