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

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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.

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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

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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.

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  1. Systems Immunology Group, Cellular and Molecular Medicine, St George’s University of London, Cranmer Terrace, London, SW17 ORE, UK

    Edit Kovalcsik, Katie Lowe, Mike Fischer, Angus Dalgleish & Mark D. Bodman-Smith

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  1. Edit Kovalcsik
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  2. Katie Lowe
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Correspondence to Mark D. Bodman-Smith.

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Kovalcsik, E., Lowe, K., Fischer, M. et al. Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation. Cancer Immunol Immunother 60, 1609–1624 (2011). https://doi.org/10.1007/s00262-011-1058-7

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