Mechanical destruction using a minimally invasive Ultrasound Needle induces anti-tumor immune responses and synergizes with the anti-PD-L1 blockade

Abstract

Immune checkpoint inhibitors (ICIs) have been widely used in treating various tumors; however, the objective response rate of ICIs is less than 40%. In this study, we attempted to induce anti-tumor immune responses using an improved ultrasonic horn device, Ultrasound Needle (UN). We tested its synergistic anti-tumor efficacy with an anti-PD-L1 antibody in a mouse tumor model. Under different parameters, UN treatment selectively induced mechanical destruction and thermal ablation effects on tumor tissues. The mechanical destruction effect of UN treatment increased the infiltration of CD8⁺ T cells in tumors and relieved the immunosuppressive tumor microenvironment. It also induced systemic anti-tumor immune responses and enhanced the therapeutic efficacy of the anti-PD-L1 antibody in both local and abscopal tumors. The mechanical destruction effect of UN treatment resulted in the release of damage-associated molecular patterns and promoted dendritic cells (DCs)-based antigen presentation. Depletion of DCs or CD8⁺ T cells eliminated the anti-tumor immune responses induced by UN treatment and weakened the synergistic anti-tumor efficacy with anti-PD-L1 antibody. Therefore, minimally invasive UN may provide a new therapeutic modality for ultrasound-assisted immunotherapy.

Keywords: Immune checkpoint inhibitor; Immunogenic cell death; Immunotherapy; Ultrasonic horn; Ultrasound.