Speaker
Description
The maintenance of healthy immune function requires a complex set of checkpoints to promote a response to genuine threats (such as cancer or infection) while recognizing benign actors to avoid chronic systemic inflammation. This process leads to a delicate balance in which stimulatory and inhibitory receptors compete to dictate a cell’s fate. Cancer cells notoriously ramp up inhibitory signaling, resulting in a lack of immune response. We explore the process of T cell exhaustion, or loss of ability to respond to a threat. Notably, we characterize the progression of T cells through their initial stimulus, activation, and subsequent exhaustion upon the earliest stages of solid tumor infiltration. We quantify, through experimental data and mechanistic modeling, activation and exhaustion scores for T cells upon encountering cancer cells. Introducing macrophages to the system presents an additional layer of complexity due to their highly plastic phenotypes, i.e., their ability to take on both an immunostimulatory and an immunosuppressive role. By characterizing T cell and macrophage activity at high resolution, we identify potential perturbations to leverage in optimizing treatment strategies for restoring a dysregulated anti-tumor immune response to a functional therapeutic state.
