title: Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.
abstract: 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.
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Tania Løve
authors.initials: TL
authors.lastname: Aaes
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaczmarek
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Physiology Group, Department of Basic Medical Sciences, Ghent University, 9000 Ghent, Belgium.
authors.forename: Tinneke
authors.initials: T
authors.lastname: Delvaeye
authors.affiliation: Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Molecular and Cellular Oncology Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: De Craene
authors.affiliation: Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Department of Pharmaceutics, Ghent University, 9000 Ghent, Belgium.
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Koker
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Heyndrickx
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Iris
authors.initials: I
authors.lastname: Delrue
authors.affiliation: Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Molecular and Cellular Oncology Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Taminau
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Wiernicki
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Groote
authors.affiliation: Cell Death Research and Therapy Lab, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, 3000 Leuven, Belgium.
authors.forename: Abhishek D
authors.initials: AD
authors.lastname: Garg
authors.affiliation: Physiology Group, Department of Basic Medical Sciences, Ghent University, 9000 Ghent, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
authors.affiliation: Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Department of Pharmaceutics, Ghent University, 9000 Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Mathieu J M
authors.initials: MJ
authors.lastname: Bertrand
authors.affiliation: Cell Death Research and Therapy Lab, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, 3000 Leuven, Belgium.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
authors.affiliation: Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Molecular and Cellular Oncology Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Declercq
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium; Methusalem Program, Ghent University, 9000 Ghent, Belgium. Electronic address: peter.vandenabeele@irc.vib-ugent.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
authors.affiliation: Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG), Ghent University, 9052 Ghent, Belgium.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Krysko
mesh_terms: D000067531:Alarmins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D007109:Immunity / Q000187:drug effects; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology; D014611:Vaccination
chemical_list: D000067531:Alarmins; D000970:Antineoplastic Agents; D018925:Chemokines; D008024:Ligands; D016328:NF-kappa B; D013752:Tetracycline