Radiation-inducible immunotherapy for cancer: senescent tumor cells as a cancer vaccine

Mol Ther. 2012 May;20(5):1046-55. doi: 10.1038/mt.2012.19. Epub 2012 Feb 14.


Radiotherapy offers an effective treatment for advanced cancer but local and distant failures remain a significant challenge. Here, we treated melanoma and pancreatic carcinoma in syngeneic mice with ionizing radiation (IR) combined with the poly(ADP-ribose) polymerase inhibitor (PARPi) veliparib to inhibit DNA repair and promote accelerated senescence. Based on prior work implicating cytotoxic T lymphocytes (CTLs) as key mediators of radiation effects, we discovered that senescent tumor cells induced by radiation and veliparib express immunostimulatory cytokines to activate CTLs that mediate an effective antitumor response. When these senescent tumor cells were injected into tumor-bearing mice, an antitumor CTL response was induced which potentiated the effects of radiation, resulting in elimination of established tumors. Applied to human cancers, radiation-inducible immunotherapy may enhance radiotherapy responses to prevent local recurrence and distant metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cellular Senescence / drug effects
  • Cellular Senescence / radiation effects
  • Combined Modality Therapy
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunotherapy / methods*
  • Lymphocyte Activation
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / mortality
  • Melanoma, Experimental / therapy*
  • Mice
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Radiation-Sensitizing Agents / pharmacology*
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured


  • Benzimidazoles
  • Cancer Vaccines
  • Cytokines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Radiation-Sensitizing Agents
  • veliparib