Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.
Document Type
Article
Publication Date
8-14-2024
Original Citation
Kim Y,
Kim G,
Kim S,
Cho B,
Kim S,
Do E,
Bae D,
Kim S,
Kweon M,
Song J,
Park S,
Hwang S,
Kim M,
Kim Y,
Min K,
Kim S,
Adams M,
Lee C,
Park H,
Park S.
Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. Cell Host Microbe. 2024;32(8):1380-93 e9.
Keywords
JGM, Fecal Microbiota Transplantation, Humans, Animals, Gastrointestinal Microbiome, Mice, Immune Checkpoint Inhibitors, Female, Male, Middle Aged, Neoplasms, Programmed Cell Death 1 Receptor, Aged, Feces, Adult, Cytokines
JAX Source
Cell Host Microbe. 2024;32(8):1380-93 e9.
ISSN
1934-6069
PMID
39059396
DOI
https://doi.org/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.