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

Despite the clear efficacy of immune checkpoint blockade, a subset of melanoma patients receives no clinical benefit from treatment. Boiling histotripsy (BH), a mechanical form of focused ultrasound, allows for non-invasive and non-ionizing tissue destruction. As mechanically fractionating tumors with BH may potentiate T cell-mediated anti-tumor responses, we addressed gaps in knowledge regarding the impact BH has on antigen-presenting cell (APC) presence in the tumor microenvironment (TME), antigen acquisition, and conventional dendritic cell (cDC) activation states in settings where BH does or does not induce a primary tumor growth response. When BH treatment immediately inhibited melanoma outgrowth, APC presence in the TME was significantly reduced, tumor antigen acquisition amongst APCs remained elevated when compared to controls, and intratumoral immune activation was observed distinctly in the cDC1 subset. Cavitation scoring based on real-time B-mode imaging signatures characteristic of BH-induced tissue destruction demonstrated that BH-mediated destruction strongly correlates with tumor antigen presence in the draining lymph nodes 24 h post-ablation. Collectively, these findings reveal that immediate BH-driven tumor growth control in a melanoma model stratifies distinct intratumoral immune states; positioning early growth response as a biologically informative prognostic indicator of BH-induced intratumoral immune activation.