Cross-reactivity between tumor MHC class I–restricted antigens and an enterococcal bacteriophage

Phages and cancer immunity Gut bacteria are involved in the education of T cell immune responses, and the intestinal ecosystem influences anticancer immunity. Fluckiger et al. report microbial antigens that might cross-react with antigens associated with tumor cells. They found that a type of intestinal bacteria called enterococci harbor a bacteriophage that modulates immune responses. In mouse models, administration of enterococci containing the bacteriophage boosted T cell responses after treatment with chemotherapy or programmed cell death protein 1 (PD-1) blockade. In humans, the presence of the bacteriophage was associated with improved survival after PD-1 immunotherapy. A fraction of human T cells specific for naturally processed melanoma epitopes appeared to be able to recognize microbial peptides. This “molecular mimicry” may represent cross-reactivity between tumors and microbial antigens. Science , this issue p. 936