High intensity focused ultrasound enhances anti-tumor immunity through promoting CD4 Th1 effector T cell response

• Main Authors: Haiying Zhang, Kun Han
• Format: Article
• Language: English
• Published: Innovation Publishing House Pte. Ltd. 2020-09-01
• Series: STEMedicine
• Subjects: Melanoma; HIFU; Anti-tumor immunity; TGFβ; MicroRNA-9-5p
• Online Access: https://stemedicine.org/index.php/stem/article/view/65

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.