Abrogation of Local Cancer Recurrence After Radiofrequency Ablation by Dendritic Cell-based Hyperthermic Tumor Vaccine

作者：Liu, Qiong; Zhai, Bo; Yang, Wen; Yu, Le-Xing; Dong, Wei; He, Ya-Qin; Chen, Lei; Tang, Liang; Lin, Yan; Huang, Dan-Dan; Wu, Hong-Ping; Wu, Meng-Chao; Yan, He-Xin; Wang, Hong-Yang^*

来源：Molecular Therapy, 2009, 17(12): 2049-2057.

DOI：10.1038/mt.2009.221

• ANTIGEN-PRESENTING CELLS
• HEPATOCELLULAR-CARCINOMA
• T-CELLS
• HEAT-SHOCK-PROTEIN-70
• COMBINATION
• ACTIVATION
• EXPRESSION
• PEPTIDES
• INNATE
• INDUCE

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-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.

• 出版日期2009-12
• 单位上海交通大学; 中国人民解放军第二军医大学