DC vaccine loaded with Bacteroides fragilis elicits functional cross-reactivity and enhances anti-PD-1 immunotherapy.

The gut microbiome profoundly influences the clinical benefits of antitumor immunotherapy. Although various gut microbiota have been shown to enhance immunotherapy, their clinical application remains unexplored. In this study, a dendritic cell (DC) vaccine loaded with the gut commensal Bacteroides fragilis (DC-Bf) was used as a therapeutic cancer vaccine. DC-Bf elicited T cell responses that recognize both B. fragilis and tumor cells, primarily via major histocompatibility complex-I-mediated cross-presentation of B. fragilis antigens to prime CD8+ T cells. DC-Bf treatment increased CD8+ T cell infiltration and activation, expanded the diversity of the T cell receptor repertoire, and reduced the proportion of regulatory T cells and M2-type tumor-associated macrophages, thereby improving the immunosuppressive tumor microenvironment. In multiple tumor-bearing models, DC-Bf enhanced the therapeutic activity of programmed cell death protein 1 inhibitors by inducing interleukin-12-driven, CD8+ T cell-dependent antitumor immune responses. This study confirms the potential of using bacteria-loaded DCs to augment immunotherapy efficacy and provides a new perspective for the clinical application of the gut microbiome. Targeting the gut microbiota holds promise as a novel avenue for developing antitumor vaccines.