Gastrointestinal Malignancies Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Liver Cancer Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Nat Rev Clin Oncol. 2023 Nov;20(11):780-798. doi: 10.1038/s41571-023-00816-4. Epub 2023 Sep 19.
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.
免疫检查点抑制剂 (ICIs) 现已广泛用于治疗晚期肝细胞癌 (HCC) 患者。两种不同的包含 ICI 的方案，阿替利珠单抗联合贝伐珠单抗和替西木单抗联合度伐利尤单抗，现已被批准为该领域的标准一线治疗方案。然而，尽管与索拉非尼相比，生存结果有了显著改善，但大多数晚期 HCC 患者并未从这些方案中获得持久的益处。包括单细胞 RNA 测序（肿瘤组织和血液样本）在内的基因组测序技术的进步，以及免疫细胞识别策略和其他技术，如放射组学和微生物组分析，为识别新的预测生物标志物创造了巨大潜力，使我们能够准确选择最有可能从 ICI 中获益的患者。在这篇综述中，我们总结了 HCC 免疫学和接受 ICI 治疗该疾病的患者结局的数据。然后，我们概述了过去 5 年中当前生物标志物的使用和发展情况，包括基因特征、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。然后讨论了 HCC 中进一步生物标志物开发的新概念，包括基于生物标志物的试验、空间转录组学和集成“大数据”分析方法。这些概念都有可能更好地识别最有可能从 ICI 中获益的患者，并促进新的治疗方法的发展。
