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Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

An Author Correction to this article was published on 08 May 2018

Abstract

Surface-exposed HSP70 and calreticulin are damage-associated molecular patterns (DAMPs) crucially involved in modulating the success of cancer therapy. Photodynamic therapy (PDT) involves the administration of a photosensitising (PTS) agent followed by visible light-irradiation. The reactive oxygen species that are thus generated directly kill tumours by damaging their microvasculature and inducing a local inflammatory reaction. PDT with the PTS photofrin is associated with DAMPs exposure, but the same is not true for other PTSs. Here, we show that when cancer cells are treated with hypericin-based PDT (Hyp-PDT), they surface-expose both HSP70 and calreticulin (CRT). Induction of CRT exposure was not accompanied by co-exposure of ERp57, but this did not compromise the ability of the exposed CRT to regulate the phagocytosis of Hyp-PDT-treated cancer cells by dendritic cells. Interestingly, we found that Hyp-PDT-induced CRT exposure (in contrast to anthracycline-induced CRT exposure) was independent of the presence of ERp57. Our results indicate that Hyp-PDT is a potential anti-cancer immunogenic modality.

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Fig. 1
Fig. 2

Abbreviations

CNTR:

Control(s)

DAMP(s):

Damage-associated molecular pattern(s)

DC:

Dendritic cells

Ecto-CRT:

Surface externalised-calreticulin

Ecto-HSP70:

Surface externalised-Heat shock protein 70

ER:

Endoplasmic reticulum

HSP:

Heat shock proteins

Hyp-PDT:

Hypericin-based photodynamic therapy

MTX:

Mitoxantrone

PDT:

Photodynamic therapy

PTS(s):

Photosensitiser(s)

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Acknowledgments

We thank Dr. Peter Carmeliet (Vesalius Research Center, VIB, Leuven, Belgium) for the CT26 cells and Dr. Natalio Garbi (German Cancer Research Center, Heidelberg, Germany) for the ERp57 WT and KO MEF cells. This work was supported by a project from the Fund for Scientific Research Flanders (FWO-Vlaanderen, G.0728.10 to P.A. and D.V.K). Research in Agostinis’ group is supported by grants from the K.U.Leuven (GOA/11/009) and FWO-Vlaanderen (G.0661.09). This paper presents research results of the IAP6/18, funded by the Interuniversity Attraction Poles Programme, initiated by the Belgian State, Science Policy Office. D.V.K. is paid by a fellowship from FWO-Vlaanderen. Research in Vandenabeele’s group is supported by VIB and Ghent University (GROUP-ID consortium of the UGent MRP initiative), FWO-Vlaanderen (G.0875.11 and G.0973.11), Federal Research Program (IAP 6/18), European Research Program FP6 ApopTrain (MRTN-CT-035624), FP7 Apo-Sys 200767, and the Euregional PACTII. P.V. holds a Methusalem grant (BOF09/01M00709) from the Flemish Government. We thank Jan Piessens for the technical support. We also thank Dr. Esther Buytaert for her help and contribution to the experiments. We would like to thank Dr. Amin Bredan for excellent editing of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cell Death Research and Therapy Unit, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University of Leuven, Campus Gasthuisberg O&N1, Herestraat 49, 3000, Leuven, Belgium

    Abhishek D. Garg & Patrizia Agostinis

  2. Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium

    Dmitri V. Krysko & Peter Vandenabeele

  3. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

    Dmitri V. Krysko & Peter Vandenabeele

Authors
  1. Abhishek D. Garg
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  2. Dmitri V. Krysko
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  3. Peter Vandenabeele
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  4. Patrizia Agostinis
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Corresponding author

Correspondence to Patrizia Agostinis.

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Garg, A.D., Krysko, D.V., Vandenabeele, P. et al. Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin. Cancer Immunol Immunother 61, 215–221 (2012). https://doi.org/10.1007/s00262-011-1184-2

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