Kim, Kim, and Kim et al. conducted a clinical trial in 13 patients with anti-PD-1-refractory advanced gastrointestinal cancers to determine if fecal microbiota transplantation (FMT) from anti-PD-1 responders could overcome resistance when combined with continued anti-PD-1 therapy. FMT induced a PR in one patient (R7) and SD in 6 additional patients. In patient R7, immune changes correlated with efficacy. Prevotella merdae Immunoactis, isolated from an anti-PD-1 responder donated to R7, was found to boost T cell activity ex vivo and decrease tumor growth in mice, while Lactobacillus salivariius and Bacteroides plebius were inhibitory to T cells.
Contributed by Katherine Turner
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.
Author Info: (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
Author Info: (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) Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea. (4) Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea. (5) Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea. (6) Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea. (7) PrismCDX Co., Ltd., Hwaseong-si 18469, Gyeonggi-do, Republic of Korea. (8) Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (9) Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (10) Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (11) Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (12) Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (13) Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (14) Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea. (15) Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea. (16) Department of Infectious Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. (17) The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. (18) The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. (19) 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: hspark27@gist.ac.kr. (20) Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: srpark@amc.seoul.kr.
