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Overview of described immune effects after irradiation of FUS in clinical studies

Year	Authors	Patient information	Ultrasound parameters	Key observations
1998	Maders-bacher et al.	5 patients with clinically localized prostate cancer	Frequency: 4.0 MHz Focal length: 2.5, 3.0, 3.5, 4.0 cm Acoustic intensity: 1,260−2,200 W/cm2 Exposure time: 4s on followed by 12s off for re-positioning.	Consistent HSP-27 expression was observed at the border zone of thermonecrosis in vivo, with highest levels occurring at 2-3 h following transrectal HIFU
2004	Wu et al.	16 patients with solid malignancies (osteosarcoma, hepatocellular carcinoma, renal cell carcinoma	Frequency: 0.8 MHz Focal length: 135 mm Acoustic intensity: 5,000−20,000 W/cm2 Exposure time: variable Therapeutic time: 2.5−8 h (median: 5.2 h)	Both the circulating CD4+ lymphocytes and the ratio of CD4+/CD8+ increased in patients after receiving HIFU
2004	Kramer et al.	6 patients with prostate cancer	Frequency: 4 MHz Focal length: not provided Acoustic intensity: 1,260−2,000 W/cm2 Exposure: 4 s per location	A significant upregulation of HSP-72 and HSP-73 at the border lesion after HIFU treatment in prostate cancer patients
2007	Wu et al.	23 patients with biopsy-proven breast cancer	Frequency: 1.6 MHz Focal length: 90 mm, Acoustic intensity: 5,000−15,000 W/cm2 Exposure time: 45-150 mins (median: 1.3 h)	All tumors treated with HIFU stained positive for epithelial membrane antigen and HSP70. No tumors treated with HIFU stained positive for CD44v6, MMP9, or PCNA
2008	Zhou et al.	15 patients with solid malignancies	Frequency: 0.8 MHz Focal length: not provided Acoustic intensity: 5,000−20,000 W/cm2 Exposure time: 0.78-3.62 h (mean: 2.74 h)	Patients exposed to complete or partial HIFU ablation experienced a reduction in serum immunosuppressive cytokine expression levels, with nonmetastatic patients experiencing lower expression levels as compared with metastatic patients. VEGF, TGF-β1, and TGF-β2 were significantly reduced following HIFU treatment
2009	Lu et al.	48 female patients with biopsy-proven breast cancer	Frequency: 1.6 MHz Focal length: not provided Acoustic intensity: 5,000−15,000 W/cm2 Exposure time: 45-150 mins (mean: 1.3 h)	Neoplasms treated with HIFU expressed elevated NK cells as well as CD3+, CD4+, CD8+, and B lymphocytes in the ablated periphery TILs positive for granzyme, FasL, and perforin were also greater in response to HIFU as compared with untreated control tumors
2009	Xu et al.	23 female patients with biopsy-proven breast cancer	Frequency: 1.6 MHz Focal length: not provided Acoustic intensity: 5,000−15,000 W/cm2 Exposure time: 45-150 min total time	A significant increase in infiltration and activation of macrophages and DCs in HIFU-treated tumors, compared to controls
2013	Wang et al.	120 patients with uterine fibroids (subserosal, intramural myomas, infertility, recurrent pregnancy loss)	Frequency: 0.8 MHz Focal length: not provided Acoustic intensity: 400 W/cm2 Exposure time: 24 h or 72 h	120 patients were divided into two groups, HIFU group and myomectomy group. Serum levels of IL-6 and IL-10 increased after treatment in both groups. Peak IL-6 and IL-10 levels were significantly lower in the HIFU group than in the myomectomy group. In contrast, IL-2 level decreased significantly in the myomectomy group compared to the HIFU group at 24 h post-operation