TITLE: “Stochasticity in cancer immunotherapies: identifying the T cell subset that sparks tumor eradication”
ABSTRACT: We use an ex vivo model of tumor eradication to dissect the fundamental variability of clinical outcomes in cancer immunotherapies. We demonstrate that there exists an inherent stochastic variability in immune responses, based on the low abundance of hyper-responsive naïve T cells (so-called Spark T cells) and feedback regulations amongst leukocytes. We introduce a methodology (combining hierarchical clustering of single-cell measurements and statistical matching with functional outcomes) to identify Spark T cells. We then carry out functional tests to model the mechanics of Spark T cells igniting global immune responses and tumor rejection.
