Boiling histotripsy induces dendritic cell activation and acquisition of antigen in tumor draining lymph nodes

Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity. However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease. Here, by applying BH to B16F10 melanoma expressing a ZsGreen antigen in a monotherapy protocol that elicits abscopal tumor control, we observed a marked increase in antigen acquisition by multiple phagocytic immune cells, including conventional dendritic cells (i.e. cDC1s and cDC2s), in tumor draining lymph nodes. Further, BH activated (CD86 expression) cDC1s and cDC2s in a tumor antigen-dependent fashion and liberated an antigen complex that likely contains a DAMP(s). In all, these results shed considerable light on how BH influences the cancer immunity cycle and offer new insight into how to best combine BH with immunotherapies.