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Cancer Immunology, Immunotherapy

, Volume 61, Issue 2, pp 215–221 | Cite as

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

  • Abhishek D. Garg
  • Dmitri V. Krysko
  • Peter Vandenabeele
  • Patrizia Agostinis
Short communication

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.

Keywords

Calreticulin HSP70 Photodynamic therapy Hypericin Cancer DAMPs 

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)

Notes

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.

Supplementary material

262_2011_1184_MOESM1_ESM.pdf (158 kb)
Supplementary material 1 (PDF 157 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Abhishek D. Garg
    • 1
  • Dmitri V. Krysko
    • 2
    • 3
  • Peter Vandenabeele
    • 2
    • 3
  • Patrizia Agostinis
    • 1
  1. 1.Cell Death Research and Therapy Unit, Department of Molecular Cell Biology, Faculty of MedicineCatholic University of LeuvenLeuvenBelgium
  2. 2.Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical ResearchVIBGhentBelgium
  3. 3.Department of Biomedical Molecular BiologyGhent UniversityGhentBelgium

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