Abrogation of local cancer recurrence after radiofrequency ablation by dendritic cell-based hyperthermic tumor vaccine

Mol Ther. 2009 Dec;17(12):2049-57. doi: 10.1038/mt.2009.221. Epub 2009 Sep 22.


Local recurrence is a therapeutic challenge for radiofrequency ablation (RFA) in treatment of small solid focal malignancies. Here we show that RFA induced heat shock proteins (HSPs) expression and high mobility group box-1 (HMGB1) translocation in xenografted melanoma, which might create a proinflammatory microenvironment that favors tumor antigen presentation and activation of the effector T cells. On this basis, we investigate whether a prime-boost strategy combining a prime with heat-shocked tumor cell lysate-pulsed dendritic cell (HT-DC) followed by an in situ boost with radiofrequency thermal ablation can prevent local tumor recurrence. The combination treatment with HT-DC and RFA showed potent antitumor effects, with >or=90% of tumor recurrence abrogated following RFA treatment. By contrast, prevaccination with unheated tumor lysate-pulsed DC had little effect on tumor relapse. Analysis of the underlying mechanism revealed that splenocytes from mice treated with HT-DC plus RFA contained significantly more tumor-specific, IFN-gamma-secreting T cells compared with control groups. Moreover, adoptive transfer of splenocytes from successfully treated tumor-free mice protected naive animals from tumor recurrence following RFA, and this was mediated mainly by CD8(+) T cells. Therefore, the optimal priming for the DC vaccination before RFA is important for boosting antigen-specific T cell responses and prevention of cancer recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Catheter Ablation*
  • Combined Modality Therapy
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Flow Cytometry
  • Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Interferon-gamma / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*


  • Cancer Vaccines
  • Heat-Shock Proteins
  • Interferon-gamma