Hepatocellular carcinoma (HCC) is a heterogeneous malignancy related to diverse etiological factors. Different oncogenic mechanisms and genetic variations lead to multiple HCC molecular classifications. Recently, an immune-based strategy using immune checkpoint inhibitors (ICIs) was presented in HCC therapy, especially with ICIs against the programmed death-1 (PD-1) and its ligand PD-L1. However, despite the success of anti-PD-1/PD-L1 in other cancers, a substantial proportion of HCC patients fail to respond. In this review, we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells (CSCs). Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to cancer. PD-L1 expression in tumoral tissues is differentially expressed in CSCs, particularly in those with a close association with the tumor microenvironment. This information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1.

中文翻译：

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肝细胞癌中针对程序性死亡-1/程序性死亡配体 1 的免疫疗法：分子变异、细胞异质性和癌症干细胞的重要性。

肝细胞癌（HCC）是一种与多种病因相关的异质性恶性肿瘤。不同的致癌机制和遗传变异导致多种 HCC 分子分类。最近，在 HCC 治疗中提出了一种使用免疫检查点抑制剂 (ICI) 的基于免疫的策略，尤其是针对程序性死亡-1 (PD-1) 及其配体 PD-L1 的 ICI。然而，尽管抗 PD-1/PD-L1 在其他癌症中取得了成功，但仍有相当大比例的 HCC 患者没有反应。在这篇综述中，我们收集了有关抗 PD-1/PD-L1 治疗的生物标志物以及 HCC 异质性和肝癌干细胞 (CSC) 的贡献的最新信息。PD-1 和 PD-L1 的遗传变异与慢性肝病和癌症进展有关。PD-L1 在肿瘤组织中的表达在 CSC 中差异表达，特别是在与肿瘤微环境密切相关的那些中。这些信息将有利于患者的选择和针对 PD-1/PD-L1 的 ICI 的管理。