title: Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin.
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.
authors.affiliation: 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.
authors.forename: Abhishek D
authors.initials: AD
authors.lastname: Garg
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Krysko
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
authors.affiliation: 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. patrizia.agostinis@med.kuleuven.be.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
mesh_terms: D000818:Animals; D000873:Anthracenes; D018943:Anthracyclines / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006414:Hematoporphyrin Photoradiation; D006801:Humans; D007249:Inflammation; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000873:Anthracenes; D018943:Anthracyclines; D017382:Reactive Oxygen Species; D010569:Perylene; C004965:hypericin; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases