Cancer Biotherapy Center, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, China.
Realbio Genomics Institute, 138 Xinjunhuan Road, Shanghai, China.
J Immunother Cancer. 2019 Jul 23;7(1):193. doi: 10.1186/s40425-019-0650-9.
Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing.
Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species.
Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making.
针对程序性死亡蛋白 1（PD-1）的检查点阻断免疫疗法最近在肝细胞癌（HCC）中显示出有希望的疗效。然而，影响和预测 HCC 患者对 PD-1 免疫治疗反应的因素仍不清楚。在此，我们使用宏基因组测序报告了 HCC 患者在接受 PD-1 免疫治疗期间肠道微生物组的动态变化特征和特异性。
对免疫治疗有反应的患者的粪便样本显示出比无反应者更高的分类丰富度和更多的基因计数。对于 PD-1 免疫治疗期间的动态分析，早在第 6 周，患者之间的β多样性差异就变得明显。在无反应者中，变形菌门从第 3 周开始增加，并在第 12 周成为主要菌门。进一步鉴定了 20 种应答富集物种，包括阿克曼氏菌和真细菌科 spp。相关功能基因和代谢途径分析，如碳水化合物代谢和产甲烷作用，验证了应答富集物种的潜在生物活性。
肠道微生物组可能对接受 PD-1 免疫治疗的 HCC 患者的反应有重要影响。肠道微生物组的动态变化特征可能为 HCC 患者免疫治疗的结果提供早期预测，这对疾病监测和治疗决策至关重要。
