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Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death

Victoria D. Turubanova, Tatiana A. Mishchenko, V Balalaeva, Irina, Iuliia Efimova (UGent) , Nina N. Peskova, Larisa G. Klapshina, Svetlana A. Lermontova, Claus Bachert (UGent) , Olga Krysko (UGent) , Maria V. Vedunova, et al.
(2021) SCIENTIFIC REPORTS. 11(1).
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Abstract
The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm(2) (lambda (ex) 615-635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.
Keywords
CALRETICULIN EXPOSURE, CANCER, IMMUNOGENIC CELL DEATH, PHOTODYNAMIC THERAPY, CALRETICULIN EXPOSURE, CANCER, MECHANISMS

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MLA
Turubanova, Victoria D., et al. “Novel Porphyrazine-Based Photodynamic Anti-Cancer Therapy Induces Immunogenic Cell Death.” SCIENTIFIC REPORTS, vol. 11, no. 1, 2021, doi:10.1038/s41598-021-86354-4.
APA
Turubanova, V. D., Mishchenko, T. A., Balalaeva, Irina, V., Efimova, I., Peskova, N. N., Klapshina, L. G., … Krysko, D. (2021). Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death. SCIENTIFIC REPORTS, 11(1). https://doi.org/10.1038/s41598-021-86354-4
Chicago author-date
Turubanova, Victoria D., Tatiana A. Mishchenko, V Balalaeva, Irina, Iuliia Efimova, Nina N. Peskova, Larisa G. Klapshina, Svetlana A. Lermontova, et al. 2021. “Novel Porphyrazine-Based Photodynamic Anti-Cancer Therapy Induces Immunogenic Cell Death.” SCIENTIFIC REPORTS 11 (1). https://doi.org/10.1038/s41598-021-86354-4.
Chicago author-date (all authors)
Turubanova, Victoria D., Tatiana A. Mishchenko, V Balalaeva, Irina, Iuliia Efimova, Nina N. Peskova, Larisa G. Klapshina, Svetlana A. Lermontova, Claus Bachert, Olga Krysko, Maria V. Vedunova, and Dmitri Krysko. 2021. “Novel Porphyrazine-Based Photodynamic Anti-Cancer Therapy Induces Immunogenic Cell Death.” SCIENTIFIC REPORTS 11 (1). doi:10.1038/s41598-021-86354-4.
Vancouver
1.
Turubanova VD, Mishchenko TA, Balalaeva, Irina V, Efimova I, Peskova NN, Klapshina LG, et al. Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death. SCIENTIFIC REPORTS. 2021;11(1).
IEEE
[1]
V. D. Turubanova et al., “Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death,” SCIENTIFIC REPORTS, vol. 11, no. 1, 2021.
@article{8709109,
  abstract     = {{The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm(2) (lambda (ex) 615-635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.}},
  articleno    = {{7205}},
  author       = {{Turubanova, Victoria D. and Mishchenko, Tatiana A. and Balalaeva, Irina, V and Efimova, Iuliia and Peskova, Nina N. and Klapshina, Larisa G. and Lermontova, Svetlana A. and Bachert, Claus and Krysko, Olga and Vedunova, Maria V. and Krysko, Dmitri}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{CALRETICULIN EXPOSURE,CANCER,IMMUNOGENIC CELL DEATH,PHOTODYNAMIC THERAPY,CALRETICULIN EXPOSURE,CANCER,MECHANISMS}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{13}},
  title        = {{Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death}},
  url          = {{http://doi.org/10.1038/s41598-021-86354-4}},
  volume       = {{11}},
  year         = {{2021}},
}
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