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Cell death stage dictates the immunogenicity of ferroptotic cancer cells

Iuliia Efimova (UGent) , Elena Catanzaro (UGent) , Robin Demuynck (UGent) , Louis Van der Meeren (UGent) , Frauke Coppieters (UGent) , Claus Bachert (UGent) , Andre Skirtach (UGent) , Olga Krysko (UGent) and Dmitri Krysko (UGent)
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Abstract
Immunotherapies hold great promise for the future treatment of cancer. It is also becoming clear that type of cancer cell death determines the antitumor immune response and, therefore, contributes to the efficiency of anti-cancer therapy and long-term survival of patients. Since tumors often develop resistance to apoptosis and necroptosis, triggering these processes is not always the optimal strategy. That is why it is crucial to select the proper cell death type potentially leading to tumor eradication. Ferroptosis, an iron-dependent form of cell death leading to lipid peroxidation in cells, is currently actively studied but whether ferroptotic cancer cells are immunogenic is unknown. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. The work on approaches to increase the immunogenicity of late ferroptotic cells is underway, which will open up novel ferroptotic cell-based experimental strategies for cancer immunotherapy. In conclusion, these results indicate that induction of ferroptosis in cancer might be another option to overcome cell death resistance and enhance the efficacy of anti-cancer therapy.
Keywords
immunogenic cell death, cancer immunotherapy, ferroptosis

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MLA
Efimova, Iuliia, et al. “Cell Death Stage Dictates the Immunogenicity of Ferroptotic Cancer Cells.” Virtual IMMUNOLOGY2021, vol. 206, no. Suppl. 1, 2021.
APA
Efimova, I., Catanzaro, E., Demuynck, R., Van der Meeren, L., Coppieters, F., Bachert, C., … Krysko, D. (2021). Cell death stage dictates the immunogenicity of ferroptotic cancer cells. Virtual IMMUNOLOGY2021, 206(Suppl. 1).
Chicago author-date
Efimova, Iuliia, Elena Catanzaro, Robin Demuynck, Louis Van der Meeren, Frauke Coppieters, Claus Bachert, Andre Skirtach, Olga Krysko, and Dmitri Krysko. 2021. “Cell Death Stage Dictates the Immunogenicity of Ferroptotic Cancer Cells.” In Virtual IMMUNOLOGY2021. Vol. 206.
Chicago author-date (all authors)
Efimova, Iuliia, Elena Catanzaro, Robin Demuynck, Louis Van der Meeren, Frauke Coppieters, Claus Bachert, Andre Skirtach, Olga Krysko, and Dmitri Krysko. 2021. “Cell Death Stage Dictates the Immunogenicity of Ferroptotic Cancer Cells.” In Virtual IMMUNOLOGY2021. Vol. 206.
Vancouver
1.
Efimova I, Catanzaro E, Demuynck R, Van der Meeren L, Coppieters F, Bachert C, et al. Cell death stage dictates the immunogenicity of ferroptotic cancer cells. In: Virtual IMMUNOLOGY2021. 2021.
IEEE
[1]
I. Efimova et al., “Cell death stage dictates the immunogenicity of ferroptotic cancer cells,” in Virtual IMMUNOLOGY2021, 2021, vol. 206, no. Suppl. 1.
@inproceedings{8729473,
  abstract     = {{Immunotherapies hold great promise for the future treatment of cancer. It is also becoming clear that type of cancer cell death determines the antitumor immune response and, therefore, contributes to the efficiency of anti-cancer therapy and long-term survival of patients. Since tumors often develop resistance to apoptosis and necroptosis, triggering these processes is not always the optimal strategy. That is why it is crucial to select the proper cell death type potentially leading to tumor eradication. Ferroptosis, an iron-dependent form of cell death leading to lipid peroxidation in cells, is currently actively studied but whether ferroptotic cancer cells are immunogenic is unknown. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. The work on approaches to increase the immunogenicity of late ferroptotic cells is underway, which will open up novel ferroptotic cell-based experimental strategies for cancer immunotherapy. In conclusion, these results indicate that induction of ferroptosis in cancer might be another option to overcome cell death resistance and enhance the efficacy of anti-cancer therapy.}},
  articleno    = {{29.13}},
  author       = {{Efimova, Iuliia and Catanzaro, Elena and Demuynck, Robin and Van der Meeren, Louis and Coppieters, Frauke and Bachert, Claus and Skirtach, Andre and Krysko, Olga and Krysko, Dmitri}},
  booktitle    = {{Virtual IMMUNOLOGY2021}},
  issn         = {{0022-1767}},
  keywords     = {{immunogenic cell death,cancer immunotherapy,ferroptosis}},
  language     = {{eng}},
  number       = {{Suppl. 1}},
  title        = {{Cell death stage dictates the immunogenicity of ferroptotic cancer cells}},
  url          = {{https://www.jimmunol.org/content/206/1_Supplement/29.13}},
  volume       = {{206}},
  year         = {{2021}},
}

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