Table 1.
Overview of described immune effects after high-intensity focused ultrasound tumor ablation in animal studies
| Authors | Year | Tumor and animal models | Treatment parameters | Main findings | Additional observations |
|---|---|---|---|---|---|
| Chapelon et al. [69] | 1992 | Dunning R3327 adenocarcinoma in Fischer Copenhagen rats |
Frequency: 1 MHz Acoustic intensity: 300–2750 W/cm2 Exposure: 3–10 s |
No recurrence of primary tumor or appearance of metastases in 14 % (Study 1) and 64 % (Study 2) of HIFU-treated animals | Lower metastatic rate in treated animals (16 vs. 28%) |
| Yang et al. [50] | 1992 | C1300 neuroblastoma in male Ajax mice |
Frequency: 4 MHz Acoustic intensity: 550 W/cm2 Exposure: 5 s per location |
Significant inhibition of tumor growth in mice treated with a thermal HIFU, compared to untreated mice | Reduced tumor growth of a secondary tumor on the contralateral side after thermal HIFU of the primary tumor |
| Hu et al. [52] | 2007 | MC-38 adenocarcinoma in C57BL/6 mice |
Frequency: 3.3 MHz Mechanical: Acoustic intensity: P+ 31.7/P− 12.5 MPa, Exposure: 30 s at 2 % duty cycle Thermal: Acoustic intensity: P+ 12/P− 6.7 MPa, Exposure: 3 s |
Thermal and mechanical HIFU increased CD11c-positive cell infiltration in tumors and accumulation of DCs in TDLNs. The antitumor effects were stronger with mechanical HIFU compared to thermal HIFU | Thermal and mechanical HIFU provide protection against subcutaneous tumor rechallenge |
| Xing et al. [53] | 2008 | B16F10 melanoma in female C57BL/6 mice |
Frequency: 3.3 MHz Mechanical: Acoustic intensity: P+ 31.7/P− 12.5 MPa, Exposure: 30 s at 2 % duty cycle Thermal: Acoustic intensity: P+ 12/P− 6.7 MPa, Exposure: 3 s |
Increased cytotoxicity of CTLs when thermal or mechanical HIFU treatment was performed 2 days before amputation of the tumor-bearing leg | Amputation of the tumor-bearing leg 2 days after thermal or mechanical HIFU resulted in a decreased metastasis incidence rate |
| Chida et al. [70] | 2009 | Sarcoma-180 in male ICR mice |
Frequency: 3 MHz Acoustic intensity: 10 W/cm2 Exposure: 10 s |
A significant reduction in tumor growth and increased survival of animals were observed after a single shot with HIFU, compared to untreated animals | Significantly higher numbers of TRAP-, CD4- and CD8-positive cells were present in tumors after HIFU treatment |
| Deng et al. [49] | 2010 | H22 hepatocellular carcinoma in C57BL/6 J mice |
Frequency: 9.5 MHz Acoustic power: 5 W Exposure: 180–240 s |
DCs loaded with HIFU-ablated tumor lysate induced significantly higher cytotoxicity and IFN-γ and TNF-α secretion by CTLs against H22 cells, than DCs loaded with untreated tumor lysate | |
| Zhang et al. [48] | 2010 | H22 hepatocellular carcinoma in C57BL/6 J mice |
Frequency: 9.5 MHz Acoustic power: 5 W Exposure: 180–240 s |
Injection of HIFU-treated tumor lysate results in an increase in tumor-specific cytotoxicity of CTLs and a significant decrease in tumor growth, compared to an injection of untreated tumor lysate | Culturing bmDCs in the presence of HIFU-treated tumor lysate slightly increased CD86, CD80 and MHCII expression and IL-12 and IFN-γ secretion, compared to untreated tumor lysate |
| Huang et al. [54] | 2012 | RM-9 prostate cancer in C57BL/6 mice |
Frequency: 3.3 MHz Acoustic intensity: P+ 32/P− 10 MPa Exposure: 20 s at 2 % duty cycle |
Mechanical HIFU, followed by resection of the tumor, inhibits growth of rechallenged tumors, increases CTL numbers in spleen and TDLN and down-regulates STAT3 levels in the tumor | |
| Liu et al. [55] | 2010 | MC-38 adenocarcinoma and B16 melanoma tumors in C57BL/6 mice |
Frequency: 3.3 MHz Acoustic intensity: P+ 19.5/P− 7.2 MPa Exposure: 4 s |
Enhanced infiltration of DCs into tumor tissue in a sparse-scan HIFU treatment regime compared to a dense-scan regime | Tumor cells heated to <55 °C in the periphery of a lesion induce more maturation of DCs than tumor cells heated to >80 °C |
| Xia et al. [51] | 2012 | H22 hepatocellular carcinoma in female C57BL/6 J mice |
Frequency: 9.5 MHz Acoustic intensity: 5 W Exposure: 220 s total time |
A significant increased cytotoxicity of CTLs and a significant increase in IFN-γ and TNF-α secretion by CTLs was observed after thermal HIFU ablation, compared to untreated controls | A significant increased number of activated tumor-specific CTLs after HIFU treatment, compared to untreated controls |
HIFU High-intensity focused ultrasound, CTLs cytotoxic T lymphocytes, TDLN tumor-draining lymph node, P+ peak-positive pressure, P− peak-negative pressure, DCs dendritic cells