%0 Journal Article
%T Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.
%A Kim Y
%A Kim G
%A Kim S
%A Cho B
%A Kim SY
%A Do EJ
%A Bae DJ
%A Kim S
%A Kweon MN
%A Song JS
%A Park SH
%A Hwang SW
%A Kim MN
%A Kim Y
%A Min K
%A Kim SH
%A Adams MD
%A Lee C
%A Park H
%A Park SR
%J Cell Host Microbe
%V 32
%N 8
%D 2024 Aug 14
%M 39059396
%F 31.316
%R 10.1016/j.chom.2024.06.010
%X 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.