{
  "abstract": "Background The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome’s impact on immune modulation is a promising area for overcoming resistance to immunotherapy.Methods This study ( NCT04130763) is an open-label, single-arm, single-center, phase I study assessing the safety and efficacy of fecal microbiota transplantation (FMT) from healthy donors in 10 patients with advanced GI cancer resistant to anti-programmed death-ligand 1 (PD-(L)1) treatment. 10 patients with histologically confirmed, unresectable, or metastatic GI cancers (8 gastric, 2 colorectal) who were refractory to anti-PD-(L)1 treatment were enrolled. Patients received initial FMT treatment via oral capsules (60 capsules), followed by a combination therapy phase, where maintenance FMT (10 capsules per treatment) was paired with nivolumab at 3 mg/kg every 2 weeks for six cycles. Serial biomarker assessments were conducted through both fecal and blood sampling.Results The combination of FMT and anti-PD-1 treatment was well tolerated with no serious adverse events. The objective response rate was 20% and the disease control rate was 40%. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Moreover, microbial signatures were identified for anti-programmed cell death protein-1 (PD-1) responsiveness and validated in an independent cohort.Conclusions This phase I study demonstrates the feasibility and safety of combining FMT with anti-PD-1 therapy in patients with ICI-refractory gastric cancer. The observed preliminary efficacy signals and identified microbial signatures generate hypotheses for future trials to investigate microbiome-based approaches to enhance immunotherapy efficacy.Trial registration number NCT04130763.",
  "authors": [
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Yifan Zhang"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Xiaomin Xu"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Shulin Wang"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Xiaochen Yin"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Bohan Zhang"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Zhengnong Zhu"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Rujie Ji"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Jing Zhu"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Hermione He"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Siyuan Cheng"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China",
        "Department of Colorectal Surgery, China-Japan Friendship Hospital, Beijing, China"
      ],
      "name": "Zihan Han"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Tong Xie"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Xiaotian Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Yakun Wang"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Si Shen"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Yan Kou"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Siyu Bao"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Yingyu Liu"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Baoran Cao"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Christophe Bonny"
    },
    {
      "affiliations": [
        "Institute for Immunology, School of Medicine, Tsinghua University, Beijing, China"
      ],
      "name": "Xiaohuan Guo"
    },
    {
      "affiliations": [
        "Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel"
      ],
      "name": "Eran Segal"
    },
    {
      "affiliations": [
        "Shenzhen Xbiome Biotech Co Ltd, Shenzhen, Guangdong, China"
      ],
      "name": "Yan Tan"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumor, Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Lin Shen"
    },
    {
      "affiliations": [
        "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumour, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China"
      ],
      "name": "Zhi Peng"
    }
  ],
  "title": "Fecal microbiota transplantation combined with anti-PD-1 therapy in refractory microsatellite-stable gastric cancer: a phase I feasibility and safety study",
  "uid": "09722f96-ec9b-5e2b-9eee-22701e3a182c"
}