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Publication : Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity.

First Author  Aaes TL Year  2016
Journal  Cell Rep Volume  15
Issue  2 Pages  274-87
PubMed ID  27050509 Mgi Jnum  J:234951
Mgi Id  MGI:5792472 Doi  10.1016/j.celrep.2016.03.037
Citation  Aaes TL, et al. (2016) Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity. Cell Rep 15(2):274-87
abstractText  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-gamma 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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