EFFECT OF HIFU ABLATION ON TUMOUR CELLS

BAHY AYOUB, MD

High-intensity focused ultrasound (HIFU) is a novel, extracorporeal non-invasive image-guided device for the treatment of benign / malignant solid and soft tumours.

Safety and feasibility were studied extensively (Illing et al. 2005 and Kennedy, 2005 and Wu, 2006). The ablation effect may be understood through the harmless passing of the ultrasound waves through human tissue, yet when focused at high intensities, sufficient energy may be deposited to produce a well demarcated volume of coagulation necrosis, independent of soft tissue type (Hill et al. 1994).

There is growing evidence of what seems to be an immunological effect as well. The results observed following the treatment of tumours by HIFU are:

  1. A subsequent reduction of secretion of immunosuppressive factors (cytokines) originating from tumour cells (Zhong et al. 2008 and Zhou et al. 2008).
  2. Activation of dendritic cells (DCs) at the periphery of the ablation site from immature to mature cells and evidence of attacking remaining tumour cells (Hu et al. 2005; Pinzon-Charry et al. 2002; Vicari et al. 2002and Zhong et al.2008).
  3. Tumour debris resulting from HIFU ablation might be a potential tumour-antigen source for the induction of host anti-tumour immune response (Rosberger et al. 1994; Wang and Sun 2002; Wu et al. 2004, 2007a; Yang et al. 1992).
  4. Significant increase of heat shock proteins (HSPs) at the tumour debris including SP60, HSP27, HSP72, HSP73 and HSP70 allowing the tumour infiltrating antigen presenting cells (APCs) to present chaperoned peptides and antigens directly to T-lymphocytes (Hu et al. 2005; Maderbacher et al. 1998; Kramer et. al. 2004 and Wu et al. 2007b).
  5. Change of gene expression of tumours.

References:
Hill CR et al. Lesion development in focused ultrasound surgery, a general model: Ultrsound Med Biol 1994; 20:259-345. Hu Z et al. Release of endogenous danger signals from HIFU-treated tumour cells and their stimulatory effects on APCs. Biochem Biophys Res Commun 2005; 335:124-131.
Illing RO et al., The safety and feasibility of extracorporeal high intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J cancer 2005; 93; 890-895.
Kennedy JF, High-intensity focused ultrasound in the treatment of solid tumours. Nat rev Cancer 2005; 5:321-327 Kramer G et al., Response to sublethal heat treatment of prostate tumour cells and of prostatic tumour infiltrating T-cells. Prostate 2004; 58: 109 - 120.
Madersbacher S et al., Regulation of heat shock protein 27 expression of prostatic cells in response to heat treatment. Prostate 1998; 37: 174-181.
Pizon-Charry A et al., Dendritic cell dysfunction in cancer. A mechanism for immunosuppression. Immuol Cell Biol 2005;83;451-461.
Rosberger DF et al., Immunomodulation in choroidal melanoma: Reversal of inverted CD4/CD8 ratios following treatment with ultrasonic hyperthermia. Biotechnol Ther 1994;5.59-68.
Vicari AP et al., Tumour escape from immune surveillance through dendritic cell inactivation. Semin Cancer Biol 2002;12:33-42
Wang X, Sun J. High-intensity ultrasound in patients with late-stage pancreactic carcinoma. Chin Med J (Engl) 2002;115:1332-1335.
Wu F et al., Activated anti-tumour immunity in cancer patients after intensity focused ultrasound ablation. Ultrasound Med Biol 2004; 30: 1217-1222.
Wu F. Extracorporeal high intensity ultrasound in the treatment of patients with solid malignancy. Minim Invasive Ther Allied Technol 2006;15:26-35.
Wu F et al., Host antitumour immune response to HIFU ablation. Int J Hyperthermia 2007 a; 23:165-171.
Wu F et al., Expression of tumour antigens and heat shock protein 70 in breast cancer cells after high intensity focused ultrasound ablation.
Ann Surg Oncol 2007b;14:1237-1242.
Yang L, Carborne DP. Tumour-host immune interactions and dendritic cell dysfunction. Adv cancer Res 2004;92:13-27.
Zhong-Lin X et al., Activation of tumour-infiltrating antigen presenting cells by intensity focused ultrasound ablation of human breast cancer. Ultrasound Med Biol 2009; 35:50-57.
Zhou Q et al., Changes in circulating immunosuppressive cytokines levels of cancer patients after high intensity focused ultrasound treatment. Ultrasound Med Biol 2008;24:81-87

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