Interrogating the Synergistic Potential of Gemcitabine and Focused Ultrasound–Induced Thermal Ablation in Breast Cancer: Insights from the BR54 Trial via Spatial Transcriptomics

Preclinical evidence indicates that combining thermal high-intensity focused ultrasound (T-FUS) with the chemotherapeutic gemcitabine (GEM) can significantly alter this TME, promoting recruitment and activation of antitumor immune cells and facilitating durable, T cell–mediated tumor control. We hypothesize that GEM preconditioning enhances T-FUS-induced inflammatory responses by reducing anti-inflammatory cell abundance in the transition zone, thereby amplifying the infiltration and activation of effector immune cells.

Leveraging the ongoing BR54 clinical trial (NCT04796220), we analyzed resected breast cancer specimens, collected approximately 14 days post-T FUS treatment, with or without prior GEM pretreatment. Using NanoString’s CosMx Spatial Molecular Imager and 1000-plex RNA panel, we performed spatially-resolved gene transcription profiling within histologically defined regions, including FUS-induced thermal lesions and adjacent tumor areas.