Dr. John Wherry is the Director of the Institute for Immunology and Immune Health at the University of Pennsylvania. He discusses how T cell exhaustion develops during chronic infections and cancer, and why it may serve as a protective adaptation rather than simply a dysfunctional immune state. He also explores how epigenetic regulation shapes exhausted T cell differentiation, the potential of emerging gene-editing and delivery technologies to manipulate T cell function, and the opportunities and limitations of artificial intelligence in advancing immunology research.