Cell state and transcription factor modulation during extended CD8+ T-cell expansion ex vivo

Adoptive cell therapy is fast becoming a cornerstone of modern tumour immunotherapy. It relies on the relatively long-term (>2 week) ex vivo expansion of T cells either in the form of tumour-infiltrating cells, or bulk cells modified with the expression of heterologous signaling proteins, e.g., chimeric antigen receptors. However, relatively little is known about the developmental trajectories of T cells under these conditions at the systems level, and whether entire genetic pathways could be manipulated for clinical advantage. Using bulk RNA-seq analysis of T cells expanded and rested over a 17-day period, we provide a resource of how gene expression changes as cells transition through distinct cellular states over the course of activation and ex-vivo expansion. We also performed experiments to investigate the role of FOSL1 in T-cell function.