Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

•Necroptotic cancer cells release DAMPs and induce dendritic cell maturation in vitro•Cross-priming of T cells was induced by necroptotic cancer cells in vivo•Necroptotic cancer cells promote the tumor antigen-specific production of IFN-γ ex vivo•Prophylactic injection of necroptotic cancer cells leads to an anti-tumor vaccination

SummarySuccessful 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.

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