When faced with a formidable foe for months on end, the immune system’s T cells begin to tire. Whether fighting a cancer or a chronic infection, they become less effective over time, a phenomenon dubbed “T cell exhaustion” by scientists. Now, researchers at Gladstone Institutes and Stanford University have revealed the genetic switches that get flipped in exhausted T cells. In the process, they discovered how to prevent this immune exhaustion—a major step toward improving immune-based treatments for cancer.