Abstract
<p>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 has been shown to result in a bolus of tumor antigen dissemination to the tumor-draining lymph nodes (TDLNs), we tested whether conventional dendritic cell (cDC) trafficking was mediating this effect and subsequent downstream T-cell responses. While we utilized two orthogonal approaches to abrogate the CCR7-CCL19/21 chemotactic gradient that cDCs use to migrate from the periphery to the TDLN, we were unable to determine whether liberated tumor antigen was making its way to the TDLNs independent of cDC trafficking. Challenges involving (i) the inconsistency of BH to impede tumor outgrowth and liberate tumor antigen, and (ii) technical variables in the bone marrow chimera systems and adoptive transfer preparations hindered our ability to draw definitive conclusions from these studies.</p>