Novel insights into HBV-hepatocellular carcinoma at single-cell sequencing

Dandan Yin, Tao Zhou, Xuyang Xia, Chang Han, Zhaoqian Liu, Qiu Li, Yang Shu, Heng Xu
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Abstract

A significant proportion of hepatocellular carcinoma (HCC) is pathologically associated with hepatitis B virus (HBV) infection, followed by unsatisfied clinical outcomes. The increasing unmet need for HBV-associated hepatocellular carcinoma (HBV-HCC) treatment drives to deeper understand the role of the intricate immune microenvironment, tumor cell plasticity and dynamics of tumor evolution in HBV-associated hepatic carcinogenesis. Thus, a comprehensive understanding of cross-talk between HBV, host cells, and tumor microenvironment is of fundamental importance for identifying immune imbalance and heterogeneity in HBV-HCC. Over the past 5 years, the application of single-cell RNA sequencing (scRNA-seq) in the understanding of heterogeneity and dynamics of immune cells, clonal evolution, and cancer stem cell (CSC) subsets of tumor cells has established a landscape for HBV-HCC tumor ecosystem. Novel insights into anatomizing immune escape mechanisms and tumor drug resistance have remarkably facilitated the revolution of HBV-HCC clinical treatment. Here, we provided a summary of HCC at single-cell resolution and details on the basic workflow, limitations, and improvements of scRNA-seq. The review highlights novel insights derived from scRNA-seq on advances in the immune microenvironment and tumor heterogeneity of HBV-HCC.

Abstract Image

单细胞测序对 HBV 肝细胞癌的新认识
相当一部分肝细胞癌(HCC)在病理上与乙型肝炎病毒(HBV)感染有关,其临床结果也不尽如人意。HBV 相关肝细胞癌(HBV-HCC)治疗需求的不断增长促使人们更深入地了解错综复杂的免疫微环境、肿瘤细胞可塑性和肿瘤演变动态在 HBV 相关肝癌发生中的作用。因此,全面了解 HBV、宿主细胞和肿瘤微环境之间的交叉对话对于识别 HBV-HCC 中的免疫失衡和异质性至关重要。过去 5 年中,单细胞 RNA 测序(scRNA-seq)在了解免疫细胞的异质性和动态、克隆进化和肿瘤细胞的癌症干细胞(CSC)亚群方面的应用,为 HBV-HCC 肿瘤生态系统建立了一个图景。对免疫逃逸机制和肿瘤耐药性的新认识极大地推动了 HBV-HCC 临床治疗的变革。在此,我们对单细胞分辨率的 HCC 进行了总结,并详细介绍了 scRNA-seq 的基本工作流程、局限性和改进之处。综述重点介绍了 scRNA-seq 对 HBV-HCC 免疫微环境和肿瘤异质性进展的新见解。
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