김수정 (광주과학기술원)

한빛사논문

조회160

광주과학기술원

Cell Host Microbe, July 25, 2024 | https://doi.org/10.1016/j.chom.2024.06.010 Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor

Yunjae Kim,^1,12 Gihyeon Kim,^1,2,12 Sujeong Kim,^1,12 Beomki Cho,¹ Sang-Yeob Kim,³ Eun-Ju Do,³ Dong-Jun Bae,⁴Seungil 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,¹Sung-Han Kim,⁹ Mark D. Adams,^10,13 Charles Lee,^10,13 Hansoo Park,^1,2,14,*and Sook Ryun Park ^11,*

¹Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea

²Genome and Company, Suwon-si 16229, Gyeonggi-do, Republic of Korea

³Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea

⁴PrismCDX Co., Ltd., Hwaseong-si 18469, Gyeonggi-do, Republic of Korea

⁵Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

⁶Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

⁷Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

⁸Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

⁹Department of Infectious Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

¹⁰The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA

¹¹Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

¹²These authors contributed equally

¹³Senior author

¹⁴Lead contact

^*Corresponding author: correspondence to Hansoo Park or Sook Ryun Park

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-26)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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