دورية أكاديمية
Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.
| العنوان: | Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. |
|---|---|
| المؤلفون: | Kim Y; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea., Kim G; 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., Kim S; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea., Cho B; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea., Kim SY; Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea., Do EJ; Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea., Bae DJ; PrismCDX Co., Ltd., Hwaseong-si 18469, Gyeonggi-do, Republic of Korea., Kim S; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Kweon MN; Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Song JS; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Park SH; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Hwang SW; Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Kim MN; Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Kim Y; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea., Min K; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea., Kim SH; Department of Infectious Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea., Adams MD; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA., Lee C; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA., Park H; 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., Park SR; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address: srpark@amc.seoul.kr. |
| المصدر: | Cell host & microbe [Cell Host Microbe] 2024 Aug 14; Vol. 32 (8), pp. 1380-1393.e9. Date of Electronic Publication: 2024 Jul 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press |
| مواضيع طبية MeSH: | Fecal Microbiota Transplantation* , Gastrointestinal Microbiome*/drug effects , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/pharmacology , Neoplasms*/immunology , Neoplasms*/therapy , Neoplasms*/microbiology , Programmed Cell Death 1 Receptor*/antagonists & inhibitors, Humans ; Animals ; Mice ; Female ; Male ; Middle Aged ; Aged ; Feces/microbiology ; Adult ; Cytokines/metabolism |
| مستخلص: | 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Bacteroides plebeius; Lactobacillus salivarius; Prevotella merdae Immunoactis; advanced solid cancer; anti-tumor immunity; fecal microbiota transplantation; gastrointestinal cancer; immune checkpoint inhibitor; metagenomics; resistance |
| المشرفين على المادة: | 0 (Immune Checkpoint Inhibitors) 0 (Programmed Cell Death 1 Receptor) 0 (PDCD1 protein, human) 0 (Cytokines) |
| تواريخ الأحداث: | Date Created: 20240726 Date Completed: 20240815 Latest Revision: 20240816 |
| رمز التحديث: | 20240817 |
| DOI: | 10.1016/j.chom.2024.06.010 |
| PMID: | 39059396 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1934-6069 |
|---|---|
| DOI: | 10.1016/j.chom.2024.06.010 |