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Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine

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Abstract
Background: Anti-cancer therapy is more successful when it can also induce an immunogenic form of cancer cell death (ICD). Therefore, when developing new treatment strategies, it is extremely important to choose methods that induce ICD and thereby activate anti-tumor immune response leading to the most effective destruction of tumor cells. The aim of this work was to analyze whether the clinically widely used photosensitizers, photosens (PS) and photodithazine (PD), can induce ICD when used in photodynamic therapy (PDT). Methods: Cell death in murine glioma GL261 or fibrosarcoma MCA205 cells was induced by PS- or PD-PDT and cell death was analyzed by MTT or flow cytometry. Intracellular distribution of PS and PD was studied by using the laser scanning microscope. Calreticulin exposure and HMGB1 and ATP release were detected by flow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of dying cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and maturation (CD11c(+)CD86(+), CD11c(+)CD40(+)) of BMDCs and production of IL-6 in the supernatant were measured. In vivo immunogenicity was analyzed in mouse tumor prophylactic vaccination model. Results: We determined the optimal concentrations of the photosensitizers and found that at a light dose of 20 J/cm(2) (lambda ex 615-635 nm) both PS and PD efficiently induced cell death in glioma GL261 and fibrosarcoma MCA205 cells. We demonstrate that PS localized predominantly in the lysosomes and that the cell death induced by PS-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) and by ferrostatin-1 and DFO (ferroptosis inhibitors), but not by the necroptosis inhibitor necrostatin-1 s. By contrast, PD accumulated in the endoplasmic reticulum and Golgi apparatus, and the cell death induced by PD-PDT was inhibited only by z-VAD-fmk. Dying cancer cells induced by PS-PDT or PD-PDT emit calreticulin, HMGB1 and ATP and they were efficiently engulfed by BMDCs, which then matured, became activated and produced IL-6. Using dying cancer cells induced by PS-PDT or PD-PDT, we demonstrate the efficient vaccination potential of ICD in vivo. Conclusions: Altogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy.
Keywords
Immunogenic cell death, ICD, Cancer, Photodynamic therapy, Ferroptosis, Ferrostatin-1, Necroptosis, Apoptosis, ANTICANCER CHEMOTHERAPY, CALRETICULIN EXPOSURE, CANCER, FERROPTOSIS, PHTHALOCYANINES, MECHANISMS, LYSOSOMES, HYPERICIN, AUTOPHAGY, DAMAGE

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MLA
Turubanova, Victoria D., et al. “Immunogenic Cell Death Induced by a New Photodynamic Therapy Based on Photosens and Photodithazine.” JOURNAL FOR IMMUNOTHERAPY OF CANCER, vol. 7, 2019, doi:10.1186/s40425-019-0826-3.
APA
Turubanova, V. D., Balalaeva, I. V., Mishchenko, T. A., Catanzaro, E., Alzeibak, R., Peskova, N. N., … Krysko, D. (2019). Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 7. https://doi.org/10.1186/s40425-019-0826-3
Chicago author-date
Turubanova, Victoria D, Irina V Balalaeva, Tatiana A Mishchenko, Elena Catanzaro, Razan Alzeibak, Nina N Peskova, Iuliia Efimova, et al. 2019. “Immunogenic Cell Death Induced by a New Photodynamic Therapy Based on Photosens and Photodithazine.” JOURNAL FOR IMMUNOTHERAPY OF CANCER 7. https://doi.org/10.1186/s40425-019-0826-3.
Chicago author-date (all authors)
Turubanova, Victoria D, Irina V Balalaeva, Tatiana A Mishchenko, Elena Catanzaro, Razan Alzeibak, Nina N Peskova, Iuliia Efimova, Claus Bachert, Elena V Mitroshina, Olga Krysko, Maria V Vedunova, and Dmitri Krysko. 2019. “Immunogenic Cell Death Induced by a New Photodynamic Therapy Based on Photosens and Photodithazine.” JOURNAL FOR IMMUNOTHERAPY OF CANCER 7. doi:10.1186/s40425-019-0826-3.
Vancouver
1.
Turubanova VD, Balalaeva IV, Mishchenko TA, Catanzaro E, Alzeibak R, Peskova NN, et al. Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine. JOURNAL FOR IMMUNOTHERAPY OF CANCER. 2019;7.
IEEE
[1]
V. D. Turubanova et al., “Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine,” JOURNAL FOR IMMUNOTHERAPY OF CANCER, vol. 7, 2019.
@article{8639590,
  abstract     = {{Background: Anti-cancer therapy is more successful when it can also induce an immunogenic form of cancer cell death (ICD). Therefore, when developing new treatment strategies, it is extremely important to choose methods that induce ICD and thereby activate anti-tumor immune response leading to the most effective destruction of tumor cells. The aim of this work was to analyze whether the clinically widely used photosensitizers, photosens (PS) and photodithazine (PD), can induce ICD when used in photodynamic therapy (PDT). 
Methods: Cell death in murine glioma GL261 or fibrosarcoma MCA205 cells was induced by PS- or PD-PDT and cell death was analyzed by MTT or flow cytometry. Intracellular distribution of PS and PD was studied by using the laser scanning microscope. Calreticulin exposure and HMGB1 and ATP release were detected by flow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of dying cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and maturation (CD11c(+)CD86(+), CD11c(+)CD40(+)) of BMDCs and production of IL-6 in the supernatant were measured. In vivo immunogenicity was analyzed in mouse tumor prophylactic vaccination model. 
Results: We determined the optimal concentrations of the photosensitizers and found that at a light dose of 20 J/cm(2) (lambda ex 615-635 nm) both PS and PD efficiently induced cell death in glioma GL261 and fibrosarcoma MCA205 cells. We demonstrate that PS localized predominantly in the lysosomes and that the cell death induced by PS-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) and by ferrostatin-1 and DFO (ferroptosis inhibitors), but not by the necroptosis inhibitor necrostatin-1 s. By contrast, PD accumulated in the endoplasmic reticulum and Golgi apparatus, and the cell death induced by PD-PDT was inhibited only by z-VAD-fmk. Dying cancer cells induced by PS-PDT or PD-PDT emit calreticulin, HMGB1 and ATP and they were efficiently engulfed by BMDCs, which then matured, became activated and produced IL-6. Using dying cancer cells induced by PS-PDT or PD-PDT, we demonstrate the efficient vaccination potential of ICD in vivo. 
Conclusions: Altogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy.}},
  articleno    = {{350}},
  author       = {{Turubanova, Victoria D and Balalaeva, Irina V and Mishchenko, Tatiana A and Catanzaro, Elena and Alzeibak, Razan and Peskova, Nina N and Efimova, Iuliia and Bachert, Claus and Mitroshina, Elena V and Krysko, Olga and Vedunova, Maria V and Krysko, Dmitri}},
  issn         = {{2051-1426}},
  journal      = {{JOURNAL FOR IMMUNOTHERAPY OF CANCER}},
  keywords     = {{Immunogenic cell death,ICD,Cancer,Photodynamic therapy,Ferroptosis,Ferrostatin-1,Necroptosis,Apoptosis,ANTICANCER CHEMOTHERAPY,CALRETICULIN EXPOSURE,CANCER,FERROPTOSIS,PHTHALOCYANINES,MECHANISMS,LYSOSOMES,HYPERICIN,AUTOPHAGY,DAMAGE}},
  language     = {{eng}},
  pages        = {{13}},
  title        = {{Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine}},
  url          = {{http://dx.doi.org/10.1186/s40425-019-0826-3}},
  volume       = {{7}},
  year         = {{2019}},
}

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