Investigating the immunomodulatory effects of histotripsy ablation for osteosarcoma

Abstract Osteosarcoma (OS) is the most common primary bone cancer in humans and dogs. Canine OS shares many biological similarities with human a valuable comparative oncology research model. In both species, metastasis remains major hurdle against improved survival, thus warranting novel therapeutic approach such as histotripsy, non-thermal, non-invasive, focused ultrasound ablation modality. Histotripsy can mechanically disintegrate gross tumor potentially induces an anti-tumor immune response to inhibit metastatic development. The objectiveof this vitro study was investigate immunomodulatory effects of histotripsy canine OS. We hypothesizedthat promotes pro-inflammatory signature monocytes macrophages. isolated CD14+ using positive selection immunomagnetic cell separation from peripheral blood mononuclear cells healthy dogs, differentiated macrophages by culturing GM-CSF for 72 hours. co-cultured histotripsy-ablated D17 24 hours, then characterized their surface markers flow cytometry performed multiplex supernatant cytokine analysis. observed upregulation CD80 CD62L on downregulation CD206 exposed compared controls, suggesting activation. decreased levels pro-tumor cytokine, TGF-β, D17s controls. Our results indicate that induce signature. This work supported grants American Kennel Club Health Foundation, Focused Ultrasound Foundation.