About this Event
Osteosarcoma Webinar Series: One of our MIB Agents OutSmarting Osteosarcoma Young Investigator 2024 grant recipients, Dr. Betsy Young, a physician-scientist from UCSF will provide an overview of her funded work: Tumor cGAS-STING repression drives immune evasion in osteosarcoma and is therapeutically targetable via host STING activation.
Osteosarcoma has an immunosuppressive macrophage-rich, T-cell depleted tumor microenvironment (TME). We have sought to identify determinants of this unique TME, focusing on dysregulation of the cGAS-STING pathway as a possible mechanism by which immune activation, which would typically occur in response to tumor genomic instability, could be repressed. Using a novel panel of patient-derived OS cell lines and paired samples, we identified a high incidence of STING repression in OS. We performed bulk RNA seq of OS cell lines treated with STING agonist, defining an OS-specific STING activation signature, which demonstrated a significant protective effect on survival in OS patient samples. In immunocompetent OS models, systemic STING agonism shows curative anti-tumor effects, shifts the tumor microenvironment towards a pro-inflammatory phenotype, and induces immunologic memory. Importantly, host STING activation is sufficient to promote this anti-tumor immunity. We have demonstrated that STING activation has anti-tumor benefit in animal models and a protective effect in the human disease, nominating this innate immune sensing pathway as an important therapeutic target in OS.
As a physician-scientist and a pediatric oncologist, Dr. Young's aim is to advance the field of pediatric oncology in her research career focused on the immunobiology of osteosarcoma. She completed her Pediatric Hematology/Oncology fellowship training at UCSF, receiving strong clinical training in high-risk pediatric solid tumors and early-phase clinical trials. Now, as a faculty member, she is investigating the pathogenesis of osteosarcoma metastasis in the Sweet-Cordero lab at UCSF, with a specific focus on immuno-oncology translational therapeutics. Her career goal is to become an independent physician-scientist with a focus on pediatric osteosarcoma immunobiology. Clinically, her area of expertise is pediatric sarcoma, and she is a member of the UCSF Pediatric Solid Tumor group. In her leisure time, she enjoys being outdoors, traveling, and running.
After a short presentation on this research, she will take questions from attendees. Share your questions in advance with us at [email protected].
Event Venue
Online
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