Low-intensity Pulsed Ultrasound Enhances NK Cell Adoptive Therapy by Modulating the Wnt/β-catenin Signaling Pathway

Renjie Feng , Ao Gu , Gökhan Zengin , Meng Du

BIO Integration ›› 2025, Vol. 6 ›› Issue (1) : 17

PDF (2331KB)
BIO Integration ›› 2025, Vol. 6 ›› Issue (1) :17 DOI: 10.15212/bioi-2025-0036
Brief Report
research-article
Low-intensity Pulsed Ultrasound Enhances NK Cell Adoptive Therapy by Modulating the Wnt/β-catenin Signaling Pathway
Author information +
History +
PDF (2331KB)

Abstract

Natural killer cell adoptive therapy is a novel immunotherapy strategy for the treatment of multiple refractory tumors, including ovarian cancer. However, natural killer cells’ anti-tumor effectiveness is limited by their viability and cytotoxicity. Our preliminary study suggested that ultrasound irradiation improves the therapeutic effects of natural killer cells on ovarian cancer through an unclear mechanism. The Wnt/β-catenin signaling pathway is a complex protein network system associated with the maturation and function of natural killer cells. Therefore, herein, to reveal the precise mechanism underlying the effects of ultrasound on natural killer cells, we measured the expression of Wnt/β-catenin signaling pathway proteins before and after ultrasound irradiation. The expression of therapeutic factors secreted by natural killer cells increased after ultrasound irradiation. Therefore, this study provides an additional strategy for optimizing the therapeutic efficiency of natural killer cells.

Keywords

Adoptive cell therapy / natural killer cells / ultrasound / Wnt/β-catenin signaling pathway

Cite this article

Download citation ▾
Renjie Feng, Ao Gu, Gökhan Zengin, Meng Du. Low-intensity Pulsed Ultrasound Enhances NK Cell Adoptive Therapy by Modulating the Wnt/β-catenin Signaling Pathway. BIO Integration, 2025, 6 (1) : 17 DOI:10.15212/bioi-2025-0036

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Konstantinopoulos PA, Matulonis UA . Clinical and translational advances in ovarian cancer therapy. Nat Cancer 2023; 4(9): 1239-57. [PMID: 37653142 DOI: 10.1038/s43018-023-00617-9]

[2]

Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov 2020; 19(3): 200-18. [PMID: 31907401 DOI: 10.1038/s41573-019-0052-1]

[3]

Vivier E, Rebuffet L, Narni-Mancinelli E, Cornen S, Igarashi RY, Fantin VR. Natural killer cell therapies. Nature 2024; 626(8000): 727-36. [PMID: 38383621 DOI: 10.1038/s41586-023-06945-1]

[4]

Lin C, Horwitz ME, Rein LAM. Leveraging natural killer cell innate immunity against hematologic malignancies: from stem cell transplant to adoptive transfer and beyond. Int J Mol Sci 2022; 24(1): 204. [PMID: 36613644 DOI: 10.3390/ijms24010204]

[5]

Shin MH, Kim J, Lim SA, Kim J, Kim SJ, et al. NK cell-based immunotherapies in cancer. Immune Netw 2020; 20(2): e14. [PMID: 32395366 DOI: 10.4110/in.2020.20.e14]

[6]

Zhu H, Blum RH, Bjordahl R, Gaidarova S, Rogers P, et al. Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity. Blood 2020; 135(6): 399-410. [PMID: 31856277 DOI: 10.1182/blood.2019000621]

[7]

Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 2018; 23(2): 181-92.e5. [PMID: 30082067 DOI: 10.1016/j.stem.2018.06.002]

[8]

Du N, Guo F, Wang Y, Cui J. NK cell therapy: a rising star in cancer treatment. Cancers (Basel) 2021; 13(16): 4129. [PMID: 34439285 DOI: 10.3390/cancers13164129]

[9]

Jiang D, Zhang J, Mao Z, Shi J, Ma P. Driving natural killer cell-based cancer immunotherapy for cancer treatment: An arduous journey to promising ground. Biomed Pharmacother. 2023; 165: 115004.

[10]

Rix A, Lederle W, Theek B, Lammers T, Moonen C, et al. Advanced ultrasound technologies for diagnosis and therapy. J Nucl Med 2018; 59(5): 740-6. [PMID: 29496981 DOI: 10.2967/jnumed.117.200030]

[11]

O’Brien WD Jr. Ultrasound-biophysics mechanisms. Prog Biophys Mol Biol 2007; 93(1-3): 212-55. [PMID: 16934858 DOI: 10.1016/j.pbiomolbio.2006.07.010]

[12]

Al Musawi MS, Jaafar MS, Al-Gailani B, Ahmed NM, Suhaimi FM, et al. Effects of low-level laser irradiation on human blood lymphocytes in vitro. Lasers Med Sci 2017; 32(2): 405-11. [PMID: 28044209 DOI: 10.1007/s10103-016-2134-1]

[13]

Bamps M, Dok R, Nuyts S. Low-level laser therapy stimulates proliferation in head and neck squamous cell carcinoma cells. Front Oncol 2018; 8: 343. [PMID: 30211121 DOI: 10.3389/fonc.2018.00343]

[14]

Huang P. An integrated approach to ultrasound imaging in medicine and biology. BIO Integration 2020; 1(3): 105-9. [DOI: 10.15212/bioi-2020-0036]

[15]

Phan TN, Fan CH, Yeh CK. Application of ultrasound to enhancing stem cells associated therapies. Stem Cell Rev Rep 2023; 19(6): 1709-25. [PMID: 37119453 DOI: 10.1007/s12015-023-10546-w]

[16]

Liang W, Liang B, Yan K, Zhang G, Zhuo J, et al. Low-intensity pulsed ultrasound: a physical stimulus with immunomodulatory and anti-inflammatory potential. Ann Biomed Eng 2024; 52(8): 1955-81. [PMID: 38683473 DOI: 10.1007/s10439-024-03523-y]

[17]

Lu P, Zhu X-Q, Xu Z-L, Zhou Q, Zhang J, et al. Increased infiltration of activated tumor-infiltrating lymphocytes after high intensity focused ultrasound ablation of human breast cancer. Surgery 2009; 145(3): 286-93. [PMID: 19231581 DOI: 10.1016/j.surg.2008.10.010]

[18]

Abe S, Nagata H, Crosby EJ, Inoue Y, Kaneko K, et al. Combination of ultrasound-based mechanical disruption of tumor with immune checkpoint blockade modifies tumor microenvironment and augments systemic antitumor immunity. J Immunother Cancer 2022; 10(1): e003717. [PMID: 35039461 DOI: 10.1136/jitc-2021-003717]

[19]

Cichocki F, Valamehr B, Bjordahl R, Zhang B, Rezner B, et al. GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity. Cancer Res 2017; 77(20): 5664-75. [PMID: 28790065 DOI: 10.1158/0008-5472.CAN-17-0799]

[20]

Tang L, An S, Zhang Z, Fan X, Guo J, et al. MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats. Bone 2021; 143: 115610. [PMID: 32829040 DOI: 10.1016/j.bone.2020.115610]

[21]

Liu S, Zhou M, Li J, Hu B, Jiang D, et al. LIPUS inhibited the expression of inflammatory factors and promoted the osteogenic differentiation capacity of hPDLCs by inhibiting the NF-κB signaling pathway. J Periodontal Res 2020; 55(1): 125-40. [PMID: 31541455 DOI: 10.1111/jre.12696]

[22]

Ma B, Hottiger MO. Crosstalk between Wnt/β-catenin and NF-κB signaling pathway during inflammation. Front Immunol 2016; 7: 378. [PMID: 27713747 DOI: 10.3389/fimmu.2016.00378]

[23]

Zhou Z, He H, Wang K, Shi X, Wang Y, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science 2020; 368(6494): eaaz7548. [PMID: 32299851 DOI: 10.1126/science.aaz7548]

[24]

Rasi V, Hameed OA, Matthey P, Bera S, Grandgenett DP, et al. Improved purification of human granzyme A/B and granulysin using a mammalian expression system. Front Immunol 2022; 13: 830290. [PMID: 35300343 DOI: 10.3389/fimmu.2022.830290]

[25]

Guan X, Guo H, Guo Y, Han Q, Li Z, et al. Perforin 1 in cancer: mechanisms, therapy, and outlook. Biomolecules 2024; 14(8): 910. [PMID: 39199299 DOI: 10.3390/biom14080910]

[26]

Laskarin G, Babarovic E, Kifer N, Bulimbasic S, Sestan M, et al. Involvement of M1-activated macrophages and perforin/granulysin expressing lymphocytes in IgA vasculitis nephritis. Int J Mol Sci 2024; 25(4): 2253. [PMID: 38396930 DOI: 10.3390/ijms25042253]

[27]

Lee IC, Wu HJ, Liu HL. Dual-frequency ultrasound induces neural stem/progenitor cell differentiation and growth factor utilization by enhancing stable cavitation. ACS Chem Neurosci 2019; 10(3): 1452-61. [PMID: 30608667 DOI: 10.1021/acschemneuro.8b00483]

[28]

Liao B, Guan M, Tan Q, Wang G, Zhang R, et al. Low-intensity pulsed ultrasound inhibits fibroblast-like synoviocyte proliferation and reduces synovial fibrosis by regulating Wnt/β-catenin signaling. J Orthop Translat 2021; 30: 41-50. [PMID: 34611513 DOI: 10.1016/j.jot.2021.08.002]

[29]

Lv Y, Zhao P, Chen G, Sha Y, Yang L. Effects of low-intensity pulsed ultrasound on cell viability, proliferation and neural differentiation of induced pluripotent stem cells-derived neural crest stem cells. Biotechnol Lett 2013; 35(12): 2201- 12. [PMID: 24078117 DOI: 10.1007/s10529-013-1313-4]

[30]

Jia L, Li D, Wei X, Chen J, Zuo D, et al. Efficacy and safety of focused low-intensity pulsed ultrasound versus pulsed shortwave diathermy on knee osteoarthritis: a randomized comparative trial. Sci Rep 2022; 12(1): 12792. [PMID: 35896688 DOI: 10.1038/s41598-022-17291-z]

[31]

Mohamad Yusoff F, Kajikawa M, Yamaji T, Kishimoto S, Maruhashi T, et al. Low-intensity pulsed ultrasound improves symptoms in patients with Buerger disease: a double-blinded, randomized, and placebo-controlled study. Sci Rep 2024; 14(1): 13704. [PMID: 38871832 DOI: 10.1038/s41598-024-64118-0]

[32]

Li W, Li X, Kong Z, Chen B, Zhou H, et al. Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia. Ultraschall Med 2023; 44(6): e274-e83. [PMID: 37467781 DOI: 10.1055/a-2133-0835]

PDF (2331KB)

6

Accesses

0

Citation

Detail

Sections
Recommended

/