Immediate Growth Control in Response to Boiling Histotripsy is Prognostic for Intratumoral Immune Activation

Area of Science:

• Oncology
• Immunology
• Biomedical Engineering

Background:

• Immune checkpoint blockade is effective for melanoma but not for all patients.
• Boiling histotripsy (BH) is a non-invasive focused ultrasound technique for tissue ablation.
• The impact of BH on the tumor microenvironment's immune cells needs further investigation.

Purpose of the Study:

• To investigate the effect of BH on antigen-presenting cells (APCs) and dendritic cells (DCs) in the melanoma tumor microenvironment (TME).
• To determine if BH-induced tumor growth response correlates with immune activation.
• To explore BH as a potential immunotherapy adjuvant.

Main Methods:

• Utilized boiling histotripsy (BH) on a melanoma model.
• Assessed APC presence, antigen acquisition, and conventional dendritic cell (cDC) activation states within the TME.
• Correlated cavitation scoring from B-mode imaging with tumor antigen presence in draining lymph nodes.
• Analyzed intratumoral immune activation in response to BH treatment.

Main Results:

• Immediate BH treatment inhibited melanoma outgrowth.
• BH reduced APC presence in the TME but maintained elevated tumor antigen acquisition.
• Intratumoral immune activation was specifically observed in the cDC1 subset.
• BH-mediated destruction correlated with tumor antigen presence in draining lymph nodes.

Conclusions:

• Immediate BH-driven tumor growth control in melanoma models indicates distinct intratumoral immune states.
• Early growth response to BH serves as a prognostic indicator for BH-induced immune activation.
• BH has the potential to potentiate T cell-mediated anti-tumor responses in melanoma.