Integrating multiplexed imaging and multiscale modeling identifies tumor phenotype conversion as a critical component of therapeutic T cell efficacy

Abstract

Cancer progression is a complex process involving interactions that unfold across molecular, cellular, and tissue scales. These multiscale interactions have been difficult to measure and to simulate. Here, we integrated CODEX multiplexed tissue imaging with multiscale modeling software to model key action points that influence the outcome of Tcell therapies with cancer. The initial phenotype of therapeutic Tcells influences the ability of Tcells to convert tumor cells to an inflammatory, anti-proliferative phenotype. This Tcell phenotype could be preserved by structural reprogramming to facilitate continual tumor phenotype conversion and killing. One takeaway is that controlling the rate of cancer phenotype conversion is critical for control of tumor growth. The results suggest new design criteria and patient selection metrics for Tcell therapies, call for a rethinking of Tcell therapeutic implementation, and provide a foundation forsynergistically integrating multiplexed imaging data with multiscale modeling of the cancer-immune interface. A record of this paper's transparent peer review process is included in the supplemental information.