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 Aug 14;32(8):1380-1393.e9. doi: 10.1016/j.chom.2024.06.010.
Yunjae Kim  1 ,  Gihyeon Kim  2 ,  Sujeong Kim  1 ,  Beomki Cho  1 ,  Sang-Yeob Kim  3 ,  Eun-Ju Do  3 ,  Dong-Jun Bae  4 ,  Seungil Kim  5 ,  Mi-Na Kweon  5 ,  Joon Seon Song  6 ,  Sang Hyoung Park  7 ,  Sung Wook Hwang  7 ,  Mi-Na Kim  8 ,  Yeongmin Kim  1 ,  Kyungchan Min  1 ,  Sung-Han Kim  9 ,  Mark D Adams  10 ,  Charles Lee  10 ,  Hansoo Park  11 ,  Sook Ryun Park  12
Affiliations
  • 1. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
  • 2. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea; Genome and Company, Suwon-si 16229, Gyeonggi-do, Republic of Korea.
  • 3. Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.
  • 4. PrismCDX Co., Ltd., Hwaseong-si 18469, Gyeonggi-do, Republic of Korea.
  • 5. Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 6. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 7. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 8. Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 9. Department of Infectious Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 10. The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • 11. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea; Genome and Company, Suwon-si 16229, Gyeonggi-do, Republic of Korea. Electronic address: [email protected].
  • 12. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: [email protected].
PMID: 39059396 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.

Keywords
Bacteroides plebeius; Lactobacillus salivarius; Prevotella merdae Immunoactis; advanced solid cancer; anti-tumor immunity; fecal microbiota transplantation; gastrointestinal cancer; immune checkpoint inhibitor; metagenomics; resistance.