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Early but not late ferroptotic cancer cells are immunogenic in vitro and in vivo

Iuliia Efimova (UGent) , Elena Catanzaro (UGent) , Louis Van der Meeren (UGent) , Claus Bachert (UGent) , Andre Skirtach (UGent) , Olga Krysko (UGent) and Dmitri Krysko (UGent)
(2021) FEBS OPEN BIO. In Febs Open Bio 11(Supplement 1). p.408-408
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Organization
Abstract
Cell-based immunotherapies hold great promise for the future treatment of cancer. The success of these therapies demonstrated the power of harnessing the immune system to eradicate tumors. It is also becoming clear that the 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 patients1. Since tumors often develop resistance to apoptosis and necroptosis, triggering these processes is not always the optimal strategy2. That is why it is crucial to find alternative ways to kill cancer cells and to select the proper immunogenic cell death type that is able to induce potent and strong anti-cancer immune responses, potentially leading to tumor eradication. Ferroptosis, an iron-dependent form of cell death leading to lipid peroxidation in cells, is currently actively studied3. We reported that cancer cells undergoing ferroptosis are immunogenic in vitro and in vivo4. Only early (not late) ferroptotic cells stimulate the phenotypic maturation of BMDCs and induce a vaccination-like effect in a tumor prophylactic vaccination model in immune-competent mice but not in immune-compromised Rag-2-/- mice. In addition, ATP and HMGB1, the best-characterized damage-associated molecular patterns that are involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as an immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. Altogether, these results identify early ferroptotic cancer cells as effective inducers of an adaptive immune response, and induction of ferroptosis in cancer might be another option to overcome cell death resistance and enhance the efficacy of anti-cancer therapy. 1. Galluzzi, L. et al.(2017) Nat. Rev. Immunol. 17, 97–111 2. Krysko, O. et al.(2017) Immunol. Rev. 280, 207–219 3. Friedmann Angeli, J. P. et al.(2019) Nat. Rev. Cancer 19, 405–414 4. Efimova, I. et al.(2020) J. Immunother. cancer 8, 1–15
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MLA
Efimova, Iuliia, et al. “Early but Not Late Ferroptotic Cancer Cells Are Immunogenic in Vitro and in Vivo.” FEBS OPEN BIO, vol. 11, no. Supplement 1, 2021, pp. 408–408.
APA
Efimova, I., Catanzaro, E., Van der Meeren, L., Bachert, C., Skirtach, A., Krysko, O., & Krysko, D. (2021). Early but not late ferroptotic cancer cells are immunogenic in vitro and in vivo. In FEBS OPEN BIO (Vol. 11, pp. 408–408). Virtual.
Chicago author-date
Efimova, Iuliia, Elena Catanzaro, Louis Van der Meeren, Claus Bachert, Andre Skirtach, Olga Krysko, and Dmitri Krysko. 2021. “Early but Not Late Ferroptotic Cancer Cells Are Immunogenic in Vitro and in Vivo.” In FEBS OPEN BIO, 11:408–408.
Chicago author-date (all authors)
Efimova, Iuliia, Elena Catanzaro, Louis Van der Meeren, Claus Bachert, Andre Skirtach, Olga Krysko, and Dmitri Krysko. 2021. “Early but Not Late Ferroptotic Cancer Cells Are Immunogenic in Vitro and in Vivo.” In FEBS OPEN BIO, 11:408–408.
Vancouver
1.
Efimova I, Catanzaro E, Van der Meeren L, Bachert C, Skirtach A, Krysko O, et al. Early but not late ferroptotic cancer cells are immunogenic in vitro and in vivo. In: FEBS OPEN BIO. 2021. p. 408–408.
IEEE
[1]
I. Efimova et al., “Early but not late ferroptotic cancer cells are immunogenic in vitro and in vivo,” in FEBS OPEN BIO, Virtual, 2021, vol. 11, no. Supplement 1, pp. 408–408.
@inproceedings{8723849,
  abstract     = {{Cell-based immunotherapies hold great promise for the future treatment of cancer. The success of these therapies demonstrated the power of harnessing the immune system to eradicate tumors. It is also becoming clear that the 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 patients1. Since tumors often develop resistance to apoptosis and necroptosis, triggering these processes is not always the optimal strategy2. That is why it is crucial to find alternative ways to kill cancer cells and to select the proper immunogenic cell death type that is able to induce potent and strong anti-cancer immune responses, potentially leading to tumor eradication. Ferroptosis, an iron-dependent form of cell death leading to lipid peroxidation in cells, is currently actively studied3. We reported that cancer cells undergoing ferroptosis are immunogenic in vitro and in vivo4. Only early (not late) ferroptotic cells stimulate the phenotypic maturation of BMDCs and induce a vaccination-like effect in a tumor prophylactic vaccination model in immune-competent mice but not in immune-compromised Rag-2-/- mice. In addition, ATP and HMGB1, the best-characterized damage-associated molecular patterns that are involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as an immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells. Altogether, these results identify early ferroptotic cancer cells as effective inducers of an adaptive immune response, and induction of ferroptosis in cancer might be another option to overcome cell death resistance and enhance the efficacy of anti-cancer therapy.
1.	Galluzzi, L. et al.(2017) Nat. Rev. Immunol. 17, 97–111
2.	Krysko, O. et al.(2017) Immunol. Rev. 280, 207–219 
3.	Friedmann Angeli, J. P. et al.(2019) Nat. Rev. Cancer 19, 405–414 
4.	Efimova, I. et al.(2020) J. Immunother. cancer 8, 1–15}},
  articleno    = {{P-08.1-24}},
  author       = {{Efimova, Iuliia and Catanzaro, Elena and Van der Meeren, Louis and Bachert, Claus and Skirtach, Andre and Krysko, Olga and Krysko, Dmitri}},
  booktitle    = {{FEBS OPEN BIO}},
  issn         = {{2211-5463}},
  keywords     = {{DEATH}},
  language     = {{eng}},
  location     = {{Virtual}},
  number       = {{Supplement 1}},
  pages        = {{P-08.1-24:408--P-08.1-24:408}},
  title        = {{Early but not late ferroptotic cancer cells are immunogenic in vitro and in vivo}},
  volume       = {{11}},
  year         = {{2021}},
}

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