Towards a Spatial Understanding: Transcriptome Profiling of the Tumor Landscape After Ablative Focused Ultrasound Regimens

Ablative Focused ultrasound (FUS) therapies are promising non-invasive techniques for localized tumor ablation that may additionally enhance systemic antitumor immunity. However, the spatial distribution of immune responses following these treatments remains limited. This study employs digital spatial transcriptome profiling to compare transcriptional changes in periablative versus distal, untargeted, regions of tumors after FUS treatement. We identified significant gene expression changes in tumors treated with either mechanical or thermal destruction modalities compared to controls, with an emphasis on upregulation of RNA processing and ribosome biogenesis pathways. Surprisingly, minimal transcriptional differences were observed between periablative and distal regions, suggesting that FUS-induced transcriptional regulation isn’t limited to the lesion periphery. Cellular deconvolution analyses revealed increased proportions of Th17 cells, dendritic cells, and CD8+ T cells in FUS-treated tumors, pointing to enhanced immune activation. Our results suggest that both mechanical and thermal FUS elicit widespread tumor transcriptional modulation and highlight the need for further investigation into their systemic and spatial bioeffects.