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Abrogation of Local Cancer Recurrence After Radiofrequency Ablation by Dendritic Cell-based Hyperthermic Tumor Vaccine
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Abrogation of Local Cancer Recurrence After Radiofrequency Ablation by Dendritic Cell-based Hyperthermic Tumor Vaccine
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Journal Article
Abrogation of Local Cancer Recurrence After Radiofrequency Ablation by Dendritic Cell-based Hyperthermic Tumor Vaccine
2009
Overview
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 ≥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-γ-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.
Publisher
Elsevier Inc,Elsevier Limited,Nature Publishing Group
Subject
/ Animals
/ Antigens
/ Cancer
/ Cancer Vaccines - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Dendritic Cells - immunology
/ Dendritic Cells - transplantation
/ Fever
/ Heat
/ Heat-Shock Proteins - metabolism
/ Interferon-gamma - metabolism
/ Male
/ Melanoma
/ Mice
/ Neoplasm Recurrence, Local - immunology
/ Neoplasm Recurrence, Local - prevention & control
/ Neoplasms, Experimental - immunology
/ Neoplasms, Experimental - therapy
/ Original
/ Surgery
/ Vaccines
