연구성과 홍보

Cell Host Microbe. 2024 Aug 14;32(8):1380-1393.e9.

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

Authors : Yunjae Kim1, Gihyeon Kim2, Sujeong Kim1, Beomki Cho1, Sang-Yeob Kim3, Eun-Ju Do3, Dong-Jun Bae4, Seungil Kim5, Mi-Na Kweon5, Joon Seon Song6, Sang Hyoung Park7, Sung Wook Hwang7, Mi-Na Kim8, Yeongmin Kim1, Kyungchan Min1, Sung-Han Kim9, Mark D Adams10, Charles Lee10, Hansoo Park11*, Sook Ryun Park12*

Affiliations :

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

2Department 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.

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 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. 

12Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

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.