Background: 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.



中文翻译：

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肝细胞癌患者肠道微生物组与免疫检查点抑制剂疗效关系的探索性研究

背景：肠道微生物组与免疫检查点抑制剂 (ICI) 在各种类型癌症患者中的疗效有关，但在肝细胞癌 (HCC) 患者中尚未发现。
目的：研究肠道微生物组与 HCC 患者 ICI 疗效之间的关系。
方法：前瞻性纳入计划接受 ICI 的 HCC 患者。在 ICI（基线）开始前 7 天内和 8 周后收集粪便样本。使用 16S rRNA 测序和鸟枪法全基因组测序评估肠道微生物组，并与客观反应（完全或部分反应）、疾病控制（客观反应或疾病稳定 ≥ 16 周）和总生存期相关。
结果：纳入 36 名 HCC 患者，其中 20 名提供基线和 8 周粪便。基线肠道微生物组的 Alpha 多样性、丰富度和组成表明响应者和非响应者之间或疾病控制组和非疾病控制组之间没有差异。对于 20 对粪便，免疫疗法没有改变任何主要的微生物组特征。在具有客观反应的患者中没有丰富特定的分类群。三种分类群——双歧杆菌属、粪球菌属和酸氨基球菌属——在疾病控制患者中富集。然而，这三个分类群的基线丰度并不能预测总体生存获益。
结论：在这项探索性研究中，我们未能揭示肠道微生物组与 ICI 对 HCC 患者的疗效有任何明显关联。需要进行更大规模的前瞻性研究才能得出明确的结论。