Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy

Area of Science:

• Oncology
• Immunology
• Nanotechnology
• Biomedical Engineering

Background:

• Poor immunogenicity of solid tumors limits the effectiveness of anti-programmed cell death protein 1 (anti-PD1) immune checkpoint blockade (ICB).
• Fewer than 30% of cancer patients respond to current ICB therapies.
• Effective strategies to enhance tumor immunogenicity are needed.

Purpose of the Study:

• To evaluate the antitumor effects of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with anti-PD1 antibodies.
• To investigate the mechanisms by which USNBs modulate the tumor immune microenvironment.
• To determine if USNBs can sensitize poorly immunogenic solid tumors to ICB.

Main Methods:

• USNBs and anti-PD1 antibody combination therapy was tested in RM1, MC38, and B16 xenograft mouse models.
• Antigen-presenting cell and CD8+ T cell phenotypes were analyzed using flow cytometry.
• Damage-associated molecular pattern (DAMP) release, antigen release, and tumor cell necrosis were assessed using western blot, flow cytometry, transmission electron microscopy, and confocal microscopy.

Main Results:

• USNBs promoted CD8+ T cell infiltration and antitumor activity.
• The combination therapy enhanced systemic antitumor immunity, induced an abscopal effect, and provided long-term immune memory post-remission.
• USNBs induced tumor cell necrosis via ultrasound cavitation, increasing DAMP and tumor antigen presentation, thereby sensitizing tumors to ICB.

Conclusions:

• USNB administration increases tumor immunogenicity by remodeling the tumor-immune microenvironment.
• USNBs represent a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy.
• This approach could improve clinical outcomes for patients with solid tumors resistant to current immunotherapies.