Cell Reports
(Apr 2016)
Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity
Tania Løve Aaes,
Agnieszka Kaczmarek,
Tinneke Delvaeye,
Bram De Craene,
Stefaan De Koker,
Liesbeth Heyndrickx,
Iris Delrue,
Joachim Taminau,
Bartosz Wiernicki,
Philippe De Groote,
Abhishek D. Garg,
Luc Leybaert,
Johan Grooten,
Mathieu J.M. Bertrand,
Patrizia Agostinis,
Geert Berx,
Wim Declercq,
Peter Vandenabeele,
Dmitri V. Krysko
Affiliations
Tania Løve Aaes
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Agnieszka Kaczmarek
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Tinneke Delvaeye
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Bram De Craene
Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium
Stefaan De Koker
Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium
Liesbeth Heyndrickx
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Iris Delrue
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Joachim Taminau
Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium
Bartosz Wiernicki
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Philippe De Groote
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Abhishek D. Garg
Cell Death Research and Therapy Lab, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, 3000 Leuven, Belgium
Luc Leybaert
Physiology Group, Department of Basic Medical Sciences, Ghent University, 9000 Ghent, Belgium
Johan Grooten
Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium
Mathieu J.M. Bertrand
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Patrizia Agostinis
Cell Death Research and Therapy Lab, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, 3000 Leuven, Belgium
Geert Berx
Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium
Wim Declercq
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Peter Vandenabeele
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
Dmitri V. Krysko
Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium
DOI
https://doi.org/10.1016/j.celrep.2016.03.037
Journal volume & issue
Vol. 15,
no. 2
Abstract
Read online
Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.
WeChat QR code
Close
