Interactions between the gut microbiome and immune system influence cancer immune surveillance, though the mechanism through which these gut-primed immune cells regulate peripheral antitumor immune response is not well understood. Now, two recent studies in Science and Science Immunology using mouse models and human tissue samples have highlighted a group of intestinal T cells with the gut-homing α4β7 integrin receptors that play a critical role in mediating response to immune checkpoint blockade cancer immunotherapy.