Baruch et al. reported that fecal microbiota transplantation (FMT) from complete responder donors and re-induction of anti-PD-1 therapy in ten anti-PD-1-refractory metastatic melanoma patients was safe, feasible, and potentially effective. Three recipients (all from one donor) demonstrated clinical responses, including one complete response and two partial responses. Tumor samples demonstrated upregulation of multiple immune-related gene sets, such as IFNγ-mediated signaling pathway, T cell activation, MHC Class II protein complex, dendritic cell differentiation, and T helper 1 type immune response, after FMT treatment.
Contributed by Shishir Pant
ABSTRACT: The gut microbiome has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. Here we performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in ten patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. Together, these early findings have important implications for modulating the gut microbiota in cancer treatment.
Author Info: (1) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. erezbaruch@mail.tau.ac.il gal.markel@sheba.health.gov.il. Department of Clinical I
Author Info: (1) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. erezbaruch@mail.tau.ac.il gal.markel@sheba.health.gov.il. Department of Clinical Immunology and Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. (2) Pediatric Division and the Microbiome Research Center, Shamir (Assaf Harofeh) Medical Center, Be'er Ya'akov, Israel. School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. (3) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (4) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (5) Department of Gastroenterology, Sheba Medical Center, Tel HaShomer, Israel. (6) Department of Gastroenterology, Hadassah Medical Center, Jerusalem, Israel. (7) Department of Mathematics, Bar Ilan University, Ramat Gan, Israel. (8) Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. (9) School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Radiological Institute, Sheba Medical Center, Tel HaShomer, Israel. (10) Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. (11) Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. (12) Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. (13) Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. (14) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (15) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (16) Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA. (17) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (18) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (19) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. (20) Infectious Diseases Unit, Assuta Ashdod University Hospital, Ashdod, Israel. (21) School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. Department of Nuclear Medicine, Sheba Medical Center, Tel HaShomer, Israel. (22) Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. (23) Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. (24) Program for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (25) Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (26) Program for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (27) School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel. (28) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. (29) Program for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (30) Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel. (31) The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. erezbaruch@mail.tau.ac.il gal.markel@sheba.health.gov.il. Department of Clinical Immunology and Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Talpiot Medical Leadership Program, Sheba Medical Center, Tel HaShomer, Israel. (32) School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA. Department of Oncology, Sheba Medical Center, Tel HaShomer, Israel.
