Leveraging spatial imaging technologies to decode cellular interactions in pancreatic cancer 3297

Abstract Description One of the core issues surrounding solid tumor cancers is the inability to predict patient responsiveness to therapies. Although tumor biopsies are common, our ability to leverage these precious tissues for treatment plans has been technologically limited, as simple histological methods have lacked the resolution to elucidate the highly variable therapeutic response outcomes within similar patient groups. Deciphering these complexities will require quantitative measurement of cellular behaviors, interactions, and phenotypes within intact tissues. Our lab has pushed to bridge the gap between spatial immunoprofiling and spatial transcriptomics. To that end, we have successfully combined the IBEX (iterative bleaching extends multiplexity) platform with HiPlex RNAscope to visualize high-plex protein markers and high-plex RNA transcripts with single-cell resolution. “Bex-Plex” enables us to perform an unmodified multi-cycle IBEX protocol on fixed frozen murine tissues followed by a modified HiPlex RNAscope protocol (so far up to 12 probes), to ensure nuclear-level alignment. With Bex-Plex we can deeply profile both the transcriptional and functional state of all cells in the tumor microenvironment, while retaining their critical spatial information. The power to profile at this single-cell level can empower predictions about the nuanced cellular interactions that drive therapeutic responsiveness, potentially revolutionizing our approach to therapy-resistant solid tumors. Funding Sources Supported by NIH/NIGMS K99/R00 GM147841-01 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)