Checkpoint inhibition, a revolutionary cancer immunotherapy, works only in a minority of patients, and scientists want to know why it is resisted in the majority. At the UC San Francisco (UCSF), scientists think they have found an answer—one that runs counter to current cancer immunotherapy dogma. These scientists say that immune cells don’t have to reach the tumor niche to encounter immune-suppressing protein, as dogma has it. Instead, immune cells may run afoul of immune-suppressing proteins carried by roving exosomes. Exosomes that sprout from cancer cells may travel through the lymphatic system or bloodstream to lymph nodes, the sites where immune cells are activated. There, the exosomes, which are packed with the immune activity–suppressing protein PD-L1, effectively disarm immune cells and prevent them from locating and attacking tumors. Details of this remote-deactivation mechanism appeared April 4 in the journal Cell, in an article entitled, “Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.” The article describes how exosomal PD-L1 acts systemically to suppress the antitumor response. The article also provides evidence that genetically blocking the remote-deactivation mechanism can promote T-cell activity in the draining lymph node, inducing systemic antitumor immunity and memory.