Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

Cell Rep. 2016 Apr 12;15(2):274-87. doi: 10.1016/j.celrep.2016.03.037. Epub 2016 Mar 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alarmins / metabolism
  • Animals
  • Antineoplastic Agents / immunology*
  • Apoptosis* / drug effects
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemokines / metabolism
  • Cross-Priming / drug effects
  • Cross-Priming / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Immunity* / drug effects
  • Ligands
  • Mice
  • Models, Biological
  • NF-kappa B / metabolism
  • Necrosis
  • Neoplasms / immunology*
  • Phagocytosis / drug effects
  • Protein Multimerization / drug effects
  • Tetracycline / pharmacology
  • Vaccination*


  • Alarmins
  • Antineoplastic Agents
  • Chemokines
  • Ligands
  • NF-kappa B
  • Tetracycline