Influence of the gut microbiota on the response to immunotherapy in hepatocellular carcinoma

Abstract

For hepatocellular carcinoma (HCC) patients, the clinical efficacy of immune checkpoint inhibitors (ICIs) remains limited by low response rates. The gut microbiome as a critical modulator of ICIs responsiveness in HCC. We systematically analyze the relevant gut microbial signatures distinguishing programmed death 1 therapy in responders and non-responders, with particular emphasis on prognostic taxa. Microbiome-targeted interventions, encompassing antibiotic modulation, probiotic supplementation, prebiotic administration, and fecal microbiota transplantation, may synergistically enhance the efficacy of ICIs by leveraging the immunomodulatory potential of gut-derived microbial metabolites. The mechanisms governing microbiome-mediated immunotherapeutic regulation involve multifaceted interactions, particularly through microbiota-driven immunomodulation within the tumor microenvironment. We identify key translational challenges of tumor heterogeneity in microbiomes. Future research directions emphasize the need for standardized protocols, longitudinal cohort studies, and innovative preclinical models to bridge existing knowledge gaps. 对肝细胞癌（HCC）患者而言，免疫检查点抑制剂（ICIs）的临床疗效受限于低响应率。肠道菌群作为HCC患者ICIs疗效的关键调节因子。我们系统分析区分PD-1治疗在响应者和非响应者中相关肠道微生物特征的，特别是关于预后菌属的。以微生物组为靶向的干预，包括抗生素调节、益生菌补充、益生元管理和粪便菌群移植，可以通过利用肠源性微生物代谢物质的免疫调节潜力，协同增强ICIs的疗效。微生物组介导的免疫治疗调节的机制涉及多方面相互作用，特别是通过肿瘤微环境内的微生物驱动免疫调节。我们确定肿瘤异质性在微生物组中的关键转化挑战。未来研究方向强调了标准化协议、纵向队列研究和创新的临床前模型，以填补现有知识空白。 Graphical abstract: [Figure not available: see fulltext.]