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Human health relies on carefully tailored communication between the immune system and commensal microbiota, a diverse community of microorganisms that naturally reside in tissues. Several commensal bacteria trigger antigen-specific T cell responses, which help control tissue homeostasis . Could such interactions be harnessed therapeutically, by engineering symbionts to prime immunity against designated targets? On page 203 of this issue, Chen et al. test this hypothesis by customizing the skin commensal Staphylococcus epidermidis to express a foreign antigen borne by melanoma cells. Upon colonization of mouse skin, these bacteria substantially bolstered organism-wide, T cell–driven attack of resulting tumors. The findings highlight the broader potential of microbiota-induced immunity toward host defense and open new doors to customized commensal bacteria therapies against a myriad of human …