Ultrasound-induced immune responses in tumors: A systematic review and meta-analysis
Open accessAbstract
Ultrasound is widely used in the diagnosis and therapy of cancer. Tumors can be treated by thermal or mechanical tissue ablation. Furthermore, tumors can be manipulated by hyperthermia, sonodynamic therapy and sonoporation, e.g., by increasing tumor perfusion or the permeability of biological barriers to enhance drug delivery. These treatments induce various immune responses in tumors. However, conflicting data and high heterogeneity between experimental settings make it difficult to generalize the effects of ultrasound on tumor immunity. Therefore, we performed a systematic review to answer the question: "Does ultrasound alter the immune reaction of peripheral solid tumors in humans and animals compared to control conditions without ultrasound?" A systematic literature search was performed in PubMed, EMBASE, and Web of Science and 24,401 potentially relevant publications were identified. Of these, 96 publications were eligible for inclusion in the systematic review. Experiments were performed in humans, rats, and mice and focused on different tumor types, primarily breast and melanoma. We collected data on thermal and non-thermal ultrasound settings, the use of sono-sensitizers or sono-enhancers, and anti-tumor therapies. Six meta-analyses were performed to quantify the effect of ultrasound on tumor infiltration by T cells (cytotoxic, helper, and regulatory T cells) and on blood cytokines (interleukin-6, interferon-γ, tumor necrosis factor-α). We provide robust scientific evidence that ultrasound alters T cell infiltration into tumors and increases blood cytokine concentrations. Furthermore, we identified significant differences in immune cell infiltration based on tumor type, ultrasound settings, and mouse age. Stronger effects were observed using hyperthermia in combination with sono-sensitizers and in young mice. The latter may impair the translational impact of study results as most cancer patients are older. Thus, our results may help refining ultrasound parameters to enhance anti-tumor immune responses for therapeutic use and to minimize immune effects in diagnostic applications.
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The "cold" tumor microenvironment inhibits immune cell activation, further reducing the effectiveness of immunotherapy-based treatments.
“Moreover, the “cold” TME inhibits immune cell activation, further reducing the effectiveness of immunotherapy-based treatments [9].”
From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [9]
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Influence of Contrast Ultrasonography With Perflutren Lipid Microspheres on Microvessel Injury
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Investigation of the Potential Immunological Effects of Boiling Histotripsy for Cancer Treatment
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Low-Intensity Focused Ultrasound Produces Immune Response in Pancreatic Cancer
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M1 Macrophage-Derived Sonoresponsive Nanoparticles for Sonodynamic Anticancer Therapy
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Observation of efficacy of TACE combined with HIFU on patients with middle-advanced liver cancer.
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Immunotherapy in colorectal cancer: an unmet need deserving of change
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Combined Treatment with Ultrasound and Immune Checkpoint Inhibitors for Prostate Cancer
Hayashi, F., Shigemura, K., Maeda, K., Hiraoka, A., Maeshige, N., Ooya, T., Sung, S., Yang, Y., & Fujisawa, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092448 · Cited by 6 · see citing works
Welfare Assessment on Healthy and Tumor-Bearing Mice after Repeated Ultrasound Imaging
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Self-citationGold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy
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Flagged first, then by citations
5 of the 144 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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Ultrasound‐Enabled Sonogenetics: Pioneering Advances in Cancer Theranostics
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- Authors
- Rix, A., Heinrichs, H., Porte, C., Leenaars, C., Bleich, A., & Kiessling, F.
- Affiliations
- RWTH Aachen University (DE)
- Medizinische Hochschule Hannover (DE)
- Fraunhofer Institute for Digital Medicine (DE)
- Corresponding author
- Kiessling, Fabian
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2024-07
- Volume
- 371
- Pages
- 146-157
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4398761272
- Cited by
- 21
- References
- 144
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 3
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen)
- Funders
- German Research Foundation (321137804, 331065168, RTG2375)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Keywords
- ultrasound, antitumor immunity, sonodynamic therapy, hyperthermia, sonoporation, T cell infiltration, cytokines, interleukin-6, interferon-gamma, TNF-α, thermal ablation, breast cancer, melanoma
- MeSH terms
- Animals, Humans, Neoplasms, Ultrasonic Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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