Cancer immunotherapy has revolutionized treatment of many forms of cancer by unleashing the immune system response against tumors. Immunotherapies that block checkpoint receptors like PD-1, proteins that limit the capacity of T cells to attack tumors, have become the choice for the treatment of numerous types of solid cancer. However, the introduction of PD-1-blocking agents can often result in T cells attacking healthy tissues in addition to cancer cells, causing severe, sometimes life-threatening, side effects that can blunt the benefits of immunotherapy. A new study reveals new insights into how PD-1 functions to maintain healthy tissues, findings that can help scientists predict, treat, or even prevent the side effects of PD-1 blocking immunotherapies.