Abstract 2198: Platform for purifying antigen-presenting myeloid cells based on frequency of interactions with T cells

Abstract Cell-cell interactions' underlying biology drives many promising therapeutic opportunities in treating cancer. However, studying cell-cell interactions is challenging because the cells are alive and remain motile, and the complexity of downstream analysis increases with every observed interaction event. Today, researchers study cell-cell interactions using a variety of commercially available spatial approaches on fixed tissue samples. While these approaches can help study regions of interest or groups of cells based on their location within the tissue sample, they don’t offer single-cell resolution and fail to provide information on the more complex behavior of said cells, including the frequency and temporal nature of their interactions. Narwhal Bio Inc.’s A1 instrument, software, and consumable platform allow for real-time cell identification, tagging, and downstream characterization of live cells in cell mixtures. The live-cell-in, live-cell-out process enables the purification of live cells based on cell behaviors for use in downstream multiomics analyses. Here, we apply this platform to study the clinically relevant T-cell activating interactions between myeloid and T cells. We screen myeloid cells presenting various concentrations and types of antigens and monitor interactions with T cells over days. Myeloid cells are tagged by the platform when in contact with T cells at multiple time intervals resulting in the ability to stratify highly involved antigen-presenting cells (APCs) from less involved APCs. The cells are then isolated live, stratified based on their level of T-cell interactions, and then subjected to further downstream characterization and assay. At the core of the presented application is the tenet that a better understanding of cell-cell interactions will expose important underlying biological pathways, thereby increasing the chance of discovering targets for therapeutic intervention. Citation Format: Eric Ferguson, Zhixuan Huang, John M. Beierle, Behrad Azimi, Kenneth H. Hu. Platform for purifying antigen-presenting myeloid cells based on frequency of interactions with T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2198.