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

Yunjae Kim·Gihyeon Kim·Sujeong Kim·Beomki Cho·Sang-Yeob Kim·Eun-Ju Do·Dong-Jun Bae·Seungil Kim·Mi-Na Kweon·Joon Seon Song·Sang Hyoung Park·Sung Wook Hwang·Mi-Na Kim·Yeongmin Kim·Kyungchan Min·Sung-Han Kim·Mark D Adams·Charles Lee·Hansoo Park·Sook Ryun Park
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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.

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AdultAnimalsFemaleHumansMaleMiceMiddle AgedCytokinesFecal Microbiota TransplantationFecesGastrointestinal MicrobiomeImmune Checkpoint InhibitorsNeoplasmsProgrammed Cell Death 1 ReceptorBacteroides plebeiusLactobacillus salivariusPrevotella merdae Immunoactisadvanced solid canceranti-tumor immunityfecal microbiota transplantationgastrointestinal cancerimmune checkpoint inhibitormetagenomicsresistanceClinical TrialJournal ArticleResearch Support, Non-U.S. Gov't

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Yunjae Kim, Gihyeon Kim, Sujeong Kim, Beomki Cho, Sang-Yeob Kim, Eun-Ju Do, Dong-Jun Bae, Seungil Kim, Mi-Na Kweon, Joon Seon Song, Sang Hyoung Park, Sung Wook Hwang, Mi-Na Kim, Yeongmin Kim, Kyungchan Min, Sung-Han Kim, Mark D Adams, Charles Lee, Hansoo Park, Sook Ryun Park. 2024-07-25. Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.. https://doi.org/10.1016/j.chom.2024.06.010

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