Leveraging Bacterial Extracellular Vesicles for Osteosarcoma Microenvironment Remodeling and Immune Activation

Presentation Description / Summary: Cancer immunotherapies have revolutionized the oncology field, however, their clinical effectiveness in treating osteosarcoma remains limited. This gap emphasizes the urgency to develop more effective immunotherapeutic strategies for osteosarcoma. Clinical evidence suggests that Staphylococcus aureus (S. aureus) infections following limb-salvage surgery are associated with improved outcomes, likely due to priming of the immune system. S. aureus produces bacterial extracellular vesicles (BEVs), a none infectious, membrane-bound structures containing proteins, and nucleic acids reflective of their bacterial origin, that have emerged as a promising platform for immunotherapy. Our research demonstrates that both wild-type and engineered S. aureus-derived BEVs exert a direct anti-tumor effect on osteosarcoma cells, including induction of cell death, disruption of immune evasion pathways, and modulation of cytokine secretion. Furthermore, we have shown that BEVs promote anti-tumor T cell polarization and are applicable in vivo. These findings support the potential of BEVs as an innovative, safe, and clinically relevant immunotherapeutic platform for osteosarcoma.