Cited by 21Ultrasound and Hyperthermia ApplicationsNanoplatforms for cancer theranosticsPhotoacoustic and Ultrasonic Imaging

Ultrasound-induced immune responses in tumors: A systematic review and meta-analysis

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Rix, Anne, Heinrichs, Helen, Porte, Céline, Leenaars, Cathalijn, Bleich, André, Kiessling, Fabian·2024·Journal of Controlled Release

Abstract

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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Crossref · 10.1016/j.jconrel.2024.05.030

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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].”

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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
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

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