{Reference Type}: Journal Article
{Title}: Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.
{Author}: Kim Y;Kim G;Kim S;Cho B;Kim SY;Do EJ;Bae DJ;Kim S;Kweon MN;Song JS;Park SH;Hwang SW;Kim MN;Kim Y;Min K;Kim SH;Adams MD;Lee C;Park H;Park SR;
{Journal}: Cell Host Microbe
{Volume}: 32
{Issue}: 8
{Year}: 2024 Aug 14
{Factor}: 31.316
{DOI}: 10.1016/j.chom.2024.06.010
{Abstract}: 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.