免疫检查点抑制剂（ICIs）现在广泛应用于晚期肝细胞癌（HCC）患者的治疗。两种不同的ICI含有方案，即阿替唑鲁莫单抗与贝伐单抗以及曲美替尤单抗与布妥珠单抗，已被批准作为标准一线治疗方法。然而，尽管与索拉非尼相比，这些方案在生存结局上有了显著改善，但大多数晚期HCC患者并未从这些方案中获得持久效益。基于基因组测序的进展，包括单细胞RNA测序（肿瘤样本和血液样本），以及免疫细胞鉴定战略和其他技术，如放射组学和微生物组分析，已为识别新型预测生物标志物提供了相当大的潜力，从而能够准确选择那些最有可能从ICI中获益的患者。在本综述中，我们总结了HCC的免疫学数据以及接受ICI治疗的患者的治疗结果。随后，我们概述了过去5年中当前生物标志物的使用和发展，包括基因签名、循环肿瘤细胞、高维流式细胞术、单细胞RNA测序以及涉及微生物组、放射组学和临床标志物的方法。接着，我们讨论了HCC生物标志物开发的新概念，包括基于生物标志物的临床试验、空间转录组学和整合的“大数据”分析方法。这些概念都有潜力更好地识别最有可能从ICI中获益的患者并促进新治疗方法的开发。© 2023. 此为美国政府作品，不受美国版权保护；可能适用外国版权保护。

Immune-checkpoint inhibitors (ICIs) are now widely used for the treatment of patients with advanced-stage hepatocellular carcinoma (HCC). Two different ICI-containing regimens, atezolizumab plus bevacizumab and tremelimumab plus durvalumab, are now approved standard-of-care first-line therapies in this setting. However, and despite substantial improvements in survival outcomes relative to sorafenib, most patients with advanced-stage HCC do not derive durable benefit from these regimens. Advances in genome sequencing including the use of single-cell RNA sequencing (both of tumour material and blood samples), as well as immune cell identification strategies and other techniques such as radiomics and analysis of the microbiota, have created considerable potential for the identification of novel predictive biomarkers enabling the accurate selection of patients who are most likely to derive benefit from ICIs. In this Review, we summarize data on the immunology of HCC and the outcomes in patients receiving ICIs for the treatment of this disease. We then provide an overview of current biomarker use and developments in the past 5 years, including gene signatures, circulating tumour cells, high-dimensional flow cytometry, single-cell RNA sequencing as well as approaches involving the microbiome, radiomics and clinical markers. Novel concepts for further biomarker development in HCC are then discussed including biomarker-driven trials, spatial transcriptomics and integrated 'big data' analysis approaches. These concepts all have the potential to better identify patients who are most likely to benefit from ICIs and to promote the development of new treatment approaches.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.