Advanced Ultrasound in Diagnosis and Therapy ›› 2025, Vol. 9 ›› Issue (3): 245-253.doi: 10.26599/AUDT.2025.240044
• Review Article • Previous Articles Next Articles
Yang Jiea, Liu Xiaodia, Wang Wenhuia, Liao Mina, Wu Zheb,c, Galeano Julyd, Perez-Buitrago Sandrae, Lu Qianga,*()
Received:
2024-08-23
Revised:
2025-03-04
Accepted:
2025-04-01
Online:
2025-09-30
Published:
2025-10-13
Contact:
Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, China. e-mail:luqiang@scu.edu.cn(Q L),
Yang Jie, Liu Xiaodi, Wang Wenhui, Liao Min, Wu Zhe, Galeano July, Perez-Buitrago Sandra, Lu Qiang. Therapeutic Focused Ultrasound: Advances in Antitumor Immunotherapy of Solid Tumors. Advanced Ultrasound in Diagnosis and Therapy, 2025, 9(3): 245-253.
Table 1
Overview of described immune effects after T-HIFU in clinical studies"
Cancer | FUS mode | Combined treatment | Parameters | Immunomodulatory effects | References |
Pancreatic carcinoma | HIFU | NA | Frequency: NA Acoustic power: 0.5-1.6 kW Duty cycle: 66% | ↑ NK cells | [ |
Prostate cancer | HIFU | NA | Frequency: 4.0 MHz Acoustic power: 1260-2000 W/cm2 Duty cycle: 100% | ↑Th1 cytokine (IL-2, IFN-γ, TNF-α) ↓Th2 cytokine (IL-4, IL-5, IL-10) | [ |
Breast cancer | HIFU | NA | Frequency: 1.6MHz Acoustic power: 5000-15000 W/cm2 Duty cycle: 100% | ↑ B cells, and NK cells ↑ HSP 70, ↑ DCs, macrophages ↑ CD3+, CD4+, CD8+, D4+/CD8+ T cells ↑ Fas ligand+, granzyme+ and perforin+ | [ |
Solid tumor (HCC, RCC) | HIFU | NA | Frequency: 0.8 MHz Acoustic power: 5000-20000 W/cm2 Duty cycle: 100% | ↑ CD4+ and the CD4+/CD8+ T cells ↓ VEGF、TGF-β1、TGF-β2 | [ |
Table 2
Overview of described immune effects after T-HIFU in preclinical studies"
Cancer | FUS mode | Combined treatment | Parameters | Immunomodulatory effects | References |
Colon cancer | HIFU | pFAR4-IL-12 | Frequency: 1.1-4.0 MHz Acoustic power: −6.7 MPa~ −10.78 MPa, 5-50 W Duty cycle: 20-100% | ↑ ATP, HSP60 ↑ DCs maturation and M1 macrophages ↑ CTLs, CD8+ T cells, memory T cells ↓ CD4+Foxp3+ T cells ↑ IFN-γ, TNF-α, IL-12 cytokines | [ |
Breast cancer | HIFU; HIFU+MnO2 HIFU+ nanobubble | TLR9 agonist; ICIs | Frequency: 1.0-9.5 MHz Acoustic power: −3.1 MPa; 5-120 W Duty cycle: 100% | ↓ MDSCs ↑ DCs maturation; ↑↓ macrophage ↑ CD8+ and CD4+ T cells ↑ IFN-γ, IL-12, TNF-α, PD-L1, IL-4 and IgG1 cytokines; ↑↓ IL-10 cytokines | [ |
HCC | HIFU; HIFU-activated T lymphocytes; Tumor debris from HIFU ablation; | NA | Frequency: 9.5 MHz Acoustic power: 5 W Duty cycle: 100% | ↑ DCs maturation; ↑ CD8+ T cells ↑ IFN-γ, IL-12, TNF-αcytokines; | [ |
Melanoma | HIFU | a-CD40 | requency: 1.5-9.3 MHz Acoustic power: −3.1 MPa~−6.7 MPa, 4.5-6 W Duty cycle: 50-100% | ↑ DCs maturation, M1 macrophage ↑ CTLs ↑ IFN-γ, TNF-α, Granzyme B+, IL-12 cytokines ↓ PD-1 expression ↓ miR-134 on CD86 | [ |
Glioblastoma | HIFU | GEVs; | Frequency: 1.1-3.5 MHz Acoustic power: 5 W; −3.1MPa Duty cycle: 100% | ↑ DCs maturation, altered macrophage polarization ↑ CD8+, CD4+ T cells ↑ IL-12p70 production ↑ Nlrp3, Jun, Mefv, IL-6 and IL-1β | [ |
Lymphoma | HIFU | NA | Frequency: 3.0 MHz Acoustic power: 35-37 W (140-148 J) | ↑ DCs maturation, ↑ PD-L1 expression | [ |
Sarcoma | HIFU | NA | Frequency: 3.0 MHz Acoustic power: 10 W/cm2 Duty cycle: 100% | ↑ Macrophages and lymphocytes | [ |
Table 3
Overview of described immune effects after M-HIFU in preclinical studies"
Cancer | FUS mode | Combined treatment | Parameters | Immunomodulatory effects | References |
Colon cancer | mHIFU | NA | Frequency: 1.1-3.3 MHz Acoustic power: −10.7~−12 MPa Duty cycle: 2-3% | ↑ ATP, HSP60 ↑ DCs maturation ↑ CTLs, ↑ IFN-γ | [ |
Prostate cancer | Boiling histotripsy | Surgery | Frequency: 3.3 MHz Acoustic power: −10 MPa Duty cycle: 2% | ↓ STAT3 activation ↑ DCs maturation ↑ CD8+ T cells; ↓CD4+ Foxp3+ T cells ↑ IFN-γ cytokines | [ |
Breast cancer | mHIFU pHIFU Histotripsy | ICIs | Frequency: 1.15-2 MHz Acoustic power: −1~−53 MPa, 200 W Duty cycle: 1-10% | TNF-induced necrosis signaling pathway and ICD effects ↑↓ MDSCs, M1, M2 macrophages ↑ CRT, HSP70, HMGB1 ↑ DCs maturation ↑ CD8+ and CD4+ T cells ↑ IFN-γ, IL-1α, IL-1β, IL-18, IL-8 cytokines; ↓ TNF-β cytokines | [ |
HCC | Histotripsy | ICIs | Frequency: 1.0 MHz Acoustic power: > −30 MPa Duty cycle: 1-2% | Necroptotic immunogenic cell death (↑pMLKL/pRIPK3, 4-HNE) ↑ ATP, HMGB1, CRT ↑ NK cells ↑DCs maturation ↑ CD8+ T cells ↓ CD4+ Foxp3+ T cells | [ |
Melanoma | Histotripsy | α-CD40 | Frequency: 1.0-3.28 MHz Acoustic power: −6~−30 MPa, 450 W Duty cycle: 1-10% | ↓ NK cells ↑Granulocytes, neutrophils, monocytes, B cells ↑ DCs, macrophages (both M1 and M2) ↑ Th cells, Tcyt, CD4+, granzyme B+ CD8+, CD8+ T cells ↑ IFN-γ cytokines; ↓ IL-10 cytokines | [ |
Glioblastoma | pHIFU+ nanobubble; Histotripsy | ICIs | Frequency: 1.1-1.5 MHz Acoustic power: −14 MPa Duty cycle: ~2% | ↑NK cells ↑ DAMPs (HMGB1, CRT) ↑ CD45+, CD8+ T cells ↓ CD4+ Foxp3+ T cells ↑ IL-2, IFN-γ cytokines; ↓ IL-10, and VEGF-α cytokines | [ |
Pancreatic cancer | pHIFU Histotripsy | Chemotherapy; ICIs; Oncolytic reovirus; α-CD40 | Frequency: 1.5 MHz Acoustic power: −16.5~ −21 MPa Duty cycle: 1% | ↑ Neutrophils ↑ HMGB1, Granzyme-B+ ↑↓ Macrophages ↑ IFN-γ+CD8+ T cells, IFN-γ+CD8+/ CD4+ Foxp3+ T cells ↓ CD4+ Foxp3+ T cells | [ |
RCC | Histotripsy | NA | Frequency: 1.5 MHz Acoustic power: −17~−20 MPa Duty cycle: 1% | ↑ HMGB1 ↑ TNF-α, IL-10, and IL-6 cytokines | [ |
Table 4
Immunomodulatory effects of therapeutic FUS in solid tumors"
Aspect | Immune response* | T-HIFU | M-HIFU |
Innate immune response | DAMPs released | ↑ ATP, HSP 60/70 | ↑ ATP, HSP 60/70, HMGB1, CRT |
NK cells, Neutrophils, Granulocytes, monocytes, B cells | ↑ B cells, NK cells | ↑ NK cells, granulocytes, neutrophils, monocytes, B cells | |
APC | ↑ DC maturation ↑↓ M1/M2 macrophages | ↑ DC maturation ↑↓ M1/M2 macrophages | |
Cytokines | ↑ IL-2, IFN-γ, TNF-α ↓ VEGF、TGF-β1、TGF-β2 | ↑ IFN-γ, IL-1α, IL-1β, IL-18, IL-8, IL-2 ↓ IL-10, VEGF-α, TNF-β | |
Adaptive immune response | CD4+, CD8+ T cells | ↑ CD3+, CD4+ and the CD4+/CD8+ T cells | ↑ CD3+, CD4+ and the CD4+/CD8+ T cells |
Cytokines | ↑ Fas ligand+, granzyme+ and perforin+ | ↑ Fas ligand+, granzyme+ and perforin+, IFN-γ+CD8+ T cells, granzyme B+ CD8+ T cells | |
Immunosuppressive microenvironment | Treg, MDSC activity | ↓ Treg, MDSC activity | ↓ Treg, MDSC activity |
Other effects | - | NA | ↑ TNF-induced necrosis signaling pathway, ICD, Necroptosis ↓ STAT3 activation |
Synergistic effects | ICIs | synergistic anti-tumor effects | synergistic anti-tumor effects |
Future direction | - | Stronger immune response | Clinical application and safety |
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