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Poster Display session 1

2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Cheol-Hee Shin

Citation

Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238

Authors

C. Shin1, K.J. Pahk2, S. Kim1, H. Kim2, S.J. Oh1

Author affiliations

  • 1 Biomedical Research Institute, Center For Biomaterials, KIST-Korea Institute of Science and Technology, 02792 - Seoul/KR
  • 2 Biomedical Research Institute, Center For Bionics, KIST-Korea Institute of Science and Technology, 02792 - Seoul/KR
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Abstract 2433

Background

Boiling histotripsy is a promising non-invasive High-Intensity Focused Ultrasound (HIFU) technique that employs HIFU mechanical effects to fractionate solid tumours without causing any signicant thermal damage. It has been suggested that boiling histotripsy may induce a strong immune response due to the absence of denatured antigenic protein at the HIFU focus. However, the underlying immunological mechanisms of this technique are poorly understood. The main objectives of this present study were to (a) investigate the feasibility of employing High-intensity Focused Ultrasound-induced Mechanical Ablation (boiling histotripsy) in the treatment of solid tumors; (b) examine the relationship between the degree of mechanical damage induced by boiling histotripsy and the level of immune activity, and (c) finally to provide a better understanding of the effects of boiling histotripsy on immune response.

Methods

In vitro 3D model system was used to investigate the effects of histotripsy on tumor immune microenvironment. MDA-MB-231 tumor spheroids were made with 10,000 cells for 72hrs and embedded in collagen gels (6mg/ml). Cell Death Pathway array was performed to determine the mechanism of tumor death. Proteome cytokine array was performed to identify antigenic factors that were secreted by damaged solid tumors. Macrophage polarization induced by immunogenic cell death was examined using qPCR array.

Results

Our results showed that cancer cells (MDA-MB-231) underwent immunogenic cell death via TNF-mediated necrosis signaling pathway after the boiling histotripsy exposure. Significant increases in secretions of damage-associated molecular patterns (CRT, HSP70, HMGB-1), pro-inflammatory cytokines (IFN-γ, IL-1α, IL-1β, IL-18) and chemokines (IL-8) which were related to M1 macrophage activation were also observed. Furthermore, the levels of these signaling proteins increased with the degree of mechanical damage induced by the boiling histotripsy.

Conclusions

We demonstrate that histotripsy causes the mechanical destruction of cancer cells and promotes immunogenic cell death, ultimately leading to an anticancer immune response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Korea Institute of Science and Technology (KIST).

Disclosure

All authors have declared no conflicts of interest.

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