{
  "abstract": "Immune checkpoint inhibition (ICI) has become a first-line treatment strategy for advanced hepatocellular carcinoma (HCC). However, treatment efficacy remains varied, and there are no reliable biomarkers of response. We used phage immunoprecipitation sequencing technology to measure circulating viral and bacterial antibodies as a biomarker of ICI response. The XGBoost Cox-proportional hazard model identified 23 viral and bacterial strains associated with survival. An antigen score developed from the 23 reactive microbial peptides significantly predicted overall survival (HR: 81.7, [95% CI]: 9.88 to 10,690.96, p<0.0001) and a high antigen score was predictive of progressive disease (HR: 4.03, [95% CI]: 0.78 to 20.87, p=0.09). The time-dependent area under the curve was 0.8 at 1 year. Findings were validated in an independent cohort and confirmed the antigen score association with survival (HR: 2.38, [95% CI 0.98 to 5.76, p=0.055). Our results suggest a unique microbial reactivity profile may serve as a potential biomarker of ICI response in patients with HCC.",
  "authors": [
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA",
        "Surgical Oncology Research Branch, Center for Cancer Institute, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Shay Behrens"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Whitney Leet Do"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Limin Wang"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Mahler Revsine"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Evan Maestri"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Aleesha Jacob"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Ching-Wen Chang"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Marshonna Forgues"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Atlas Mashayekhi Sardoo"
    },
    {
      "affiliations": [
        "Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Anuradha Budhu"
    },
    {
      "affiliations": [
        "Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra, Pamplona, Spain",
        "Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain",
        "RNA and DNA Therapy Program, Centro de Investigación Medica Aplicada (CIMA), Pamplona, Spain"
      ],
      "name": "Josepmaria Argemí"
    },
    {
      "affiliations": [
        "Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra, Pamplona, Spain"
      ],
      "name": "Miguel Sogbe"
    },
    {
      "affiliations": [
        "Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra, Pamplona, Spain",
        "Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain"
      ],
      "name": "Bruno Sangro"
    },
    {
      "affiliations": [
        "Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA",
        "Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Tim F Greten"
    },
    {
      "affiliations": [
        "Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA",
        "Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Xin Wei Wang"
    }
  ],
  "title": "Pan-microbial serological repertoire as a biomarker of immunotherapy response in hepatocellular carcinoma",
  "uid": "ac5de99d-5e2d-5b34-8d05-95f31659152e"
}