Combination of gamma-irradiation and dendritic cell administration induces a potent antitumor response in tumor-bearing mice: approach to treatment of advanced stage cancer

Int J Cancer. 2001 Dec 15;94(6):825-33. doi: 10.1002/1097-0215(20011215)94:6<825::aid-ijc1545>;2-5.


We investigated a new approach to the treatment of advanced stage cancer, a combination of apoptosis-inducing therapy and dendritic cell (DC) administration. MethA sarcoma and C3 tumor containing defined tumor-specific antigens in form of peptides' epitopes were selected as experimental mouse models. Sites of established subcutaneous tumors were gamma-irradiated with 10 Gy 3-5 times with 4-5 day interval. DCs generated from bone marrow of syngeneic mice were injected i.v. and s.c. after each irradiation. A large number of cell tracker-labeled DCs accumulated at the site of the irradiated tumor after s.c. injections. This effect was not observed in non-irradiated tumors. Almost all of these DCs bound GFP-labeled MethA cells in tumor tissue. Interferon-gamma production by splenocytes in response to the tumor-specific MHC class I matched peptides was determined by ELISPOT assays. The combination of gamma-irradiation and DC administration, but not each of the treatments alone resulted in a significant increase in T cell response to the specific, but not to the control peptides. An increased proportion of tumor peptide-specific CD8(+)-cells was found only in that group of mice using staining with tetramers. DCs with defective presentation of antigen via MHC class I or MHC class II pathways were unable to induce peptide-specific T cell response. The combination of gamma-irradiation and DC administration but not each of the treatments alone resulted in a dramatic antitumor effect. A substantial proportion of mice completely rejected their tumors (80% in case of MethA sarcoma and 40% in case of C3 tumor). In the rest of the mice, tumor growth was notably suppressed or completely blocked. These data suggest that the combination of apoptosis-inducing therapy and DC administration may be an attractive approach to the treatment of advanced cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Apoptosis*
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Female
  • Gamma Rays
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*


  • Interferon-gamma