Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

Publication date: Available online 31 March 2016
Source:Cell Reports
Author(s): 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
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.

Graphical abstract

Teaser

Løve Aaes et al. show that necroptotic cancer cells induce the maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using RIPK3 induction systems, the authors further demonstrate efficient prophylactic vaccination with immunogenic necroptotic cells.


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