Dendritic Cells Loaded with Ultrasound-Ablated Tumour Induce in vivo Specific Antitumour Immune Responses

Abstract 

Previous studies have shown that high-intensity focused ultrasound (HIFU) ablation can induce a local inflammation with marked infiltration of dendritic cells (DCs). The purpose of this study was to investigate whether DCs could capture and present activating signals delivered by necrotic tumour cells that remain in situ after HIFU, thus initiating specific antitumour immunity. Tumour debris was derived from a mouse H22 tumour model after HIFU ablation. Bone marrow-derived DCs were loaded with HIFU-treated tumour, tumour lysate and mouse serum. Syngeneic naïve C57BL/6J mice were immunised with three loaded DCs followed by a subsequent H22 tumour challenge. Tumour size and survival were then recorded in each vaccinated mouse. The results showed that both HIFU-ablated tumour and tumour lysate could significantly increase the number of mature DCs and the secretion of IL-12 and IFN-γ (p<0.001). The proliferation of splenic lymphocytes co-incubated with the loaded-DCs was significantly higher in both HIFU-ablated tumour and tumour lysate groups (p<0.01). Cytotoxocity and TNF-α and IFN-γ secretion of cytotoxic T lymphocytes against H22 cells were significantly higher in HIFU-ablated tumour group than that in tumour lysate group (p<0.01). After the H22 tumour challenge, a significant decrease of tumour volume was observed in HIFU-ablated tumour group (p<0.01). However, there was no statistical difference of long-term survival rates among three groups (p>0.05). It is concluded that DCs can be activated by HIFU-ablated tumour debris and, thus, initiate host specific antitumour immune response after HIFU therapy. (E-mail: mfengwu@yahoo.com)

Key Words: High-intensity focused ultrasound, Neoplasm, Ultrasound, Therapy, Dendritic cell, Vaccine, Immune response, Thermal ablation, Immunotherapy