Journal of Hepatocellular Carcinoma (Jul 2021)

An Exploratory Study for the Association of Gut Microbiome with Efficacy of Immune Checkpoint Inhibitor in Patients with Hepatocellular Carcinoma

  • Shen YC,
  • Lee PC,
  • Kuo YL,
  • Wu WK,
  • Chen CC,
  • Lei CH,
  • Yeh CP,
  • Hsu C,
  • Hsu CH,
  • Lin ZZ,
  • Shao YY,
  • Lu LC,
  • Liu TH,
  • Chen CH,
  • Wu MS,
  • Huang YH,
  • Cheng AL

Journal volume & issue
Vol. Volume 8
pp. 809 – 822

Abstract

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Ying-Chun Shen,1,2,* Pei-Chang Lee,3,4,* Yu-Lun Kuo,5 Wei-Kai Wu,6 Chieh-Chang Chen,7 Chengh-Hau Lei,7 Ching-Ping Yeh,8 Chiun Hsu,1,2 Chih-Hung Hsu,2,8 Zhong-Zhe Lin,1,8 Yu-Yun Shao,2,8 Li-Chun Lu,2,8 Tsung-Hao Liu,2,8 Chien-Hung Chen,7,9 Ming-Shiang Wu,7,10 Yi-Hsiang Huang,4,11,* Ann-Lii Cheng1,10,* 1Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; 2Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan; 4Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5Biotools Co., Ltd, New Taipei City, Taiwan; 6Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; 7Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 8Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 9Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Taipei, Taiwan; 10Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 11Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ann-Lii ChengNational Taiwan University Cancer Center, No. 57, Ln. 155, Sec. 3, Keelung Road, Da-an Dist., Taipei City, 106, TaiwanEmail [email protected] HuangDepartment of Internal Medicine, Taipei Veterans General Hospital, Taipei, TaiwanEmail [email protected]: Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC).Aims: To investigate the association between gut microbiome and efficacy of ICI in patients with HCC.Methods: Patients with HCC who were scheduled to receive ICI were prospectively enrolled. Fecal samples were collected within 7 days before initiation of ICI (baseline) and 8 weeks later. Gut microbiome was assessed using 16S rRNA sequencing and shotgun whole-genome sequencing and correlated with objective response (complete or partial response), disease control (objective response or stable disease for ≥ 16 weeks), and overall survival.Results: Thirty-six patients with HCC were enrolled, and 20 of them provided both baseline and 8-week feces. Alpha diversity, richness, and compositions of baseline gut microbiome indicated no difference between responders and nonresponders or between disease control and nondisease control groups. For the 20 paired feces, immunotherapy did not change any of the major microbiome features. No specific taxa were enriched in patients with objective response. Three taxa—Bifidobacterium, Coprococcus, and Acidaminococcus—were enriched in patients with disease control. However, the baseline abundance of these three taxa did not predict overall survival benefit.Conclusions: In this exploratory study, we failed to disclose any overt association of gut microbiome with the efficacy of ICI in patients with HCC. A larger prospective study is warranted for definite conclusion.Keywords: gut microbiome, biomarkers, immune checkpoint inhibitor, hepatocellular carcinoma

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