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.
Resources from the same session
1267 - Genetic landscape of KEAP1 and NFE2L2 mutated cancers from the AACR GENIE database
Presenter: Mark Zaki
Session: Poster Display session 1
Resources:
Abstract
878 - β-arrestin1 is involved in the Ras-induced malignant transformation
Presenter: Takashi Shibano
Session: Poster Display session 1
Resources:
Abstract
4143 - Incidence of second cancer among PLWHIV: retrospective observational study of a series of 601 patients in the French CANCERVIH network
Presenter: Jean-Philippe Spano
Session: Poster Display session 1
Resources:
Abstract
5145 - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: the CUPISCO trial experience
Presenter: Chantal Pauli
Session: Poster Display session 1
Resources:
Abstract
1737 - Incidence and Outcome of chronic lymphocytic leukemia with Deletion 17p: An Indian experience; challenges and opportunities
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
2596 - Driving solo? Investigation into collaborating mutations in SDH-deficient neoplasia
Presenter: Jonathan Killian
Session: Poster Display session 1
Resources:
Abstract
1499 - The potential of a novel antiangiogenic VEGFR1-D2 binding peptide in oncology therapeutics
Presenter: Afsaneh Sadre Momtaz
Session: Poster Display session 1
Resources:
Abstract
1775 - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors
Presenter: Mayu Yunokawa
Session: Poster Display session 1
Resources:
Abstract
4584 - First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumors: Dose-optimization cohorts
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract