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

  • Edit Kovalcsik
  • Katie Lowe
  • Mike Fischer
  • Angus Dalgleish
  • Mark D. Bodman-SmithEmail author
Original article

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.

Keywords

Dendritic cells Tumour cells Apoptosis Poly(I:C) T helper cell type 1 

Abbreviations

IFN-γ

Interferon-gamma

dsRNA

Double stranded RNA

IFN-γ/poly(I:C) tumour cell

IFN-γ pre-treated and poly(I:C) pulsed or loaded tumour cell

Notes

Acknowledgments

This work was supported by funding from the Fischer Family Trust (1075453), and the Cancer Vaccine Institute. The authors would like to thank Dr Jayne Dennis and Dr Gary Coulton of the SGUL Biomics Unit for technical assistance and helpful discussion.

Supplementary material

262_2011_1058_MOESM1_ESM.pdf (536 kb)
Supplementary material 1 (PDF 536 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Edit Kovalcsik
    • 1
  • Katie Lowe
    • 1
  • Mike Fischer
    • 1
  • Angus Dalgleish
    • 1
  • Mark D. Bodman-Smith
    • 1
    Email author
  1. 1.Systems Immunology Group, Cellular and Molecular MedicineSt George’s University of LondonLondonUK

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