Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers. [Display omitted] •FMT with anti-PD-1 shows benefits in advanced solid cancers resistant to anti-PD-1•FMT induced partial response to anti-PD-1 in R7 recipients with enhanced immunity•Lactobacillus salivarius and Bacteroides plebeius may inhibit T cell activity•Prevotella merdae Immunoactis boosts T cell activity and reduces tumor growth Kim et al. show that fecal microbiota transplantation combined with anti-PD-1 therapy can overcome resistance in advanced solid cancers. They identify Prevotella merdae Immunoactis, which enhances immune response and inhibits tumor growth, while confirming two non-efficacious strains that may inhibit T cell activity, suggesting that specific microbiota could improve immunotherapy effectiveness.