The study made use of high intensity focused ultrasound (HIFU), a novel technique were ultrasonic waves are directed to specific areas of the body to heat and eliminate unhealthy tissue. In the past decade, this technique has emerged as a cutting-edge procedure in the treatment of uterine fibroids and cancer.
While the mechanical aspects of the technique are well understood, the subsequent biological responses had not been thoroughly evaluated. This prompted the Duke researchers to assess if this technique was having any secondary effects on the host's biological defense systems. Specifically, they wanted to evaluate if HIFU therapy could stimulate an anti-tumour immune response.
For their study, the researchers utilized mice that were implanted with cancer cells that later developed into adenocarcinoma colon tumours. The mice were then subjected to either low- intensity or high-intensity HIFU. This would allow the researchers to differentiate between mechanical versus heat-damage ultrasound effects. As a measure of immune reactivity, the team followed the function of dendritic (surveillance) cells as well as tumour growth in the mice. When the research team evaluated dendritic cell (DC) activity, they found that both thermal and mechanical HIFU increased the number of DCs significantly by a factor 3.1 and 4-fold, respectively. As a control, the team injected mice directly with cultured DCs and found that it only increased their levels by 1.5-fold as compared to untreated (and intact) mice.
As an indication that immune recognition was taking place, the researchers next evaluated the movement of DCs to lymph nodes, the processing centers of the immune system. Here they found that thermal HIFU increased the accumulation of DCs by a factor of 5. In comparison, mechanical HIFU increased the level DCs by a factor of 10.
When the research team evaluated tumour elimination, they found that thermal and mechanical HIFU could decrease the volume of tumours in mice by 85 and 43%, respectively. More importantly, they were able to observe that both methods generated a strong immune response as evidenced by mice rejecting tumours when they were injected under their skin.
The researchers conveyed that these findings suggest that focused mechanical (low-intensity) ultrasound treatment has the capacity to generate an immune response to tumours via the activation of dendritic cells.
In the Duke press release, professor Zhong state that "our results show that while mechanical HIFU is not as effective as thermal HIFU in killing tumour cells directly, it has the potential to induce a stronger antitumour immune response. These preliminary findings open up the possibility that we could use heat from HIFU to treat the primary tumour and HIFU-boosted immunotherapy for combating any residual and metastatic tumour cells.
OF INTEREST IS THAT BOTH THE DUKE TEAM AND PROFESSOR SLAVIN, UNKNOWN TO EACH OTHER, CAME TO THE SAME CONCLUSION.
Sources:
Journal of Translational Medicine: http://www.translational-medicine.com/content/5/1/34
Duke News: http://pratt.duke.edu/news/?id=1035