Intestinal microbiota have been proposed to induce commensal-specific memory T cells
that cross-react with tumor-associated antigens. We identified major histocompatibility
complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP)
of a prophage found in the genome of the bacteriophage Enterococcus hirae Mice bearing
E. hirae harboring this prophage mounted a TMP-specific H-2Kb-restricted CD8+ T lymphocyte
response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration
of bacterial strains engineered to express the TMP epitope improved immunotherapy
in mice. In renal and lung cancer patients, the presence of the enterococcal prophage
in stools and expression of a TMP-cross-reactive antigen by tumors correlated with
long-term benefit of PD-1 blockade therapy. In melanoma patients, T cell clones recognizing
naturally processed cancer antigens that are cross-reactive with microbial peptides
were detected.
