Immunotherapy has redefined cancer treatment, but not all patients experience the same benefit when treated. New research in mice identifies how gut bacteria alter the body’s response to a common form of cancer immunotherapy. The animals’ gut microbiota lowered the expression of two immune molecules, one previously unknown to play a role in cancer. • Using antibodies to block the activity of either molecule, or the interplay between them, enhanced response to cancer immunotherapy. • The findings can inform the design of treatments that boost the efficacy of cancer immunotherapy among patients with suboptimal response.