While there are currently several immune-based therapeutics available for the treatment of melanoma, a large number of patients do not respond to treatment. This is often attributed to a poor pre-treatment anti-tumor immune response, and it has been postulated that increasing this baseline immune activity may enhance the efficacy of these immunotherapeutics as well as increase the percentage of responders. It has been shown that high-intensity ultrasound generates an increased anti-tumor immune response, although the mechanisms by which this occurs are poorly understood. In our lab, we have developed a low-intensity microbubble-enhanced ultrasound protocol that provides improved melanoma growth control and animal survival. To understand the mechanisms controlling ultrasound-mediated tumor growth control, we’ve performed flow cytometry on treated tumors and showed that ultrasound increases the infiltration of regulatory T cells, helper T cells, cytotoxic T cells, natural killer cells and macrophages. To determine which cell type is responsible for ultrasound-mediated tumor growth control, we have performed experiments examining the growth of ultrasound vs. untreated tumors in Rag-1 knock out mice (lacking an adaptive immune system), performed flow cytometry on ultrasound treated animals who have received tagged T cells, and performed flow cytometry on ultrasound treated animals who have received FTY720 (which prevented T cell trafficking). With these approaches, we are distinguishing the effects of the adaptive vs. the innate immune system, as well as the contributions of T cell proliferation vs. trafficking, in ultrasound-mediated tumor growth control.

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