Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response
- PDF / 1,456,250 Bytes
- 14 Pages / 595.28 x 793.7 pts Page_size
- 22 Downloads / 173 Views
RESEARCH
Open Access
Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response Hao-Li Liu1, Han-Yi Hsieh1, Li-An Lu1, Chiao-Wen Kang2, Ming-Fang Wu3 and Chun-Yen Lin2*
Abstract Background: High-intensity focused-ultrasound (HIFU) has been successfully employed for thermal ablation of tumors in clinical settings. Continuous- or pulsed-mode HIFU may also induce a host antitumor immune response, mainly through expansion of antigen-presenting cells in response to increased cellular debris and through increased macrophage activation/infiltration. Here we demonstrated that another form of focused ultrasound delivery, using low-pressure, pulsed-mode exposure in the presence of microbubbles (MBs), may also trigger an antitumor immunological response and inhibit tumor growth. Methods: A total of 280 tumor-bearing animals were subjected to sonographically-guided FUS. Implanted tumors were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the permeability of tumor microvasculature. Results: Tumor progression was suppressed by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was inhibited. Conclusions: Our findings suggest that low-pressure FUS exposure with MBs may constitute a useful tool for triggering an anticancer immune response, for potential cancer immunotherapy.
Background The potential use of focused ultrasound for cancer treatment has long been recognized. Continuous-wave (CW) high-intensity focused ultrasound (HIFU) is a particularly promising approach to rapidly produce high temperatures at the target site, resulting in necrosis of tumor cells [1-4]. Ultrasonic energy emitted from concave piezoelectric ceramics can be tightly focused with radial and axial dimensions of only 1–2 mm and 10–20 mm, respectively, based on the range of frequencies and transducer geometry, so multiple sonications are required to achieve complete tumor ablation [2-6]. CW-HIFU has been successfully applied for non-malignant-cancer treatment, such as partial ablation of uterine fibroids for symptomatic
* Correspondence: [email protected] 2 Department of Hepatogastroenterology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan Full list of author information is available at the end of the article
high-precision targeted ablation in the brain [3,10,11]. Medical imaging can be used to guide ablation of malignant solid tumors in breast cancer [12,13], prostate cancer [14], pancreatic cancer [6], or liver cancer [13,15], by introduction of multiple “cigar”-shaped thermal lesions to avoid leaving any residual tumor behind. Mounting evidence suggests that in addition to thermal ablation of cancer cells, HIFU may also boost the host antitumor immune response including CD4+/CD8+ related tumor-infiltrating lymphocytes (TILs) [16,17], dendritic
Data Loading...
