Abstract
Background: Melanoma accounts for more than 80% of deaths from all dermatologic cancers, mainly due to its widespread metastasis. High intensity focused ultrasound (HIFU) is a promising technique for cancer therapy. Here, we investigated the efficacy of HIFU against melanoma and the underlying mechanisms.
 Methods: A melanoma allograft mouse model was established to examine the tumor progression and survival rate. Anti-tumor immunity was determined by measuring cytokines, regulatory T cells (Tregs), Th17 cells and CD8+ effector T cells. Western blot, qPCR, RNAi and luciferase assay were performed to confirm the expression and regulation of microRNA (miR)-9-5p and transforming growth factor beta (TGF-β).
 Results: HIFU exposure significantly suppressed melanoma growth and metastasis by activating interferon gamma (IFN-γ) secretion, inhibiting Tregs and Th17 cells, and stimulating CD8+ effector T cells. TGF-β was a direct target of miR-9-5p. The anti-tumor effect of HIFU might be mediated through the miR-9-5p/TGF-β pathway.
 Conclusion: HIFU activates anti-tumor response and alters tumor microenvironment, which may serve as a potential therapeutic strategy for melanoma treatment.
Highlights
Melanoma develops from the melanocytes and is the most malignant type of skin cancer
The melanoma tumor bearing mice were administrated with sham-High intensity focused ultrasound (HIFU) or HIFU, respectively, hematoxylin eosin (H&E) staining result showed that the cell proliferation of melanoma in HIFU exposure mice was slowed down compared to that in the sham group mice (Figure 1A)
We further investigated the pulmonary metastasis in mice with primary tumors after B16-F10 cell intravenous injection, as shown in Figure 1C, HIFU exposure markedly reduced the number of tumor nodules in the lung compared to the sham-HIFU treatment (19 vs 34, P < 0.01)
Summary
Melanoma develops from the melanocytes and is the most malignant type of skin cancer. Melanoma accounts for only 4% of skin cancers, it causes more than 80% of deaths from all dermatologic cancers [1, 2]. The major cause of death is widespread metastasis [3]. Development of effective therapy to inhibit the growth and metastasis have crucial importance in melanoma treatment. Uchida et al reported that the HIFU therapy improved prostate cancer outcomes, and the 10-year survival rate reached 89.6% among 918 patients [11].Breast cancer is an ideal target for HIFU treatment due to its superficial position.The. Melanoma accounts for more than 80% of deaths from all dermatologic cancers, mainly due to its widespread metastasis. We investigated the efficacy of HIFU against melanoma and the underlying mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
