乙型肝炎病毒(HBV)感染在肝脏相关病理的病因和进展中发挥重要作用,包括慢性肝炎,纤维化,肝硬化,和最终的肝细胞癌(HCC)。值得注意的是,HBV感染是驱动HCC发展的主要病因。鉴于HBV感染对肝脏疾病的重大贡献,全面了解肝脏微环境中的免疫动力学,跨越慢性HBV感染,纤维化,肝硬化,和HCC,是必不可少的。在这次审查中,我们重点研究了从HBV感染到HCC的致病性肝微环境中CD8+T细胞的功能改变。我们彻底回顾了缺氧的作用,酸性pH,代谢重编程,氨基酸缺乏,抑制性检查点分子,免疫抑制细胞因子,和肠-肝通讯在肝脏微环境中形成CD8T细胞功能障碍。这些因素对临床预后有显著影响。此外,我们全面回顾了基于CD8+T细胞的肝病治疗策略,包括HBV感染,纤维化,肝硬化,和HCC。策略包括免疫检查点封锁,代谢性T细胞靶向治疗,治疗性T细胞疫苗接种,和基因工程CD8+T细胞的过继转移,以及程序性细胞死亡蛋白-1/程序性死亡配体-1(PD-1/PD-L1)抑制剂与线粒体靶向抗氧化剂的联合使用。鉴于在乙型肝炎病毒诱导的肝细胞癌(HBV+HCC)的各个阶段靶向CD8+T细胞显示出希望,我们回顾了正在进行的研究,以阐明CD8+T细胞和肝脏微环境之间的复杂相互作用之间的HBV感染发展为HCC。我们还讨论了个性化治疗方案,结合治疗策略和利用肠道微生物群调节,这具有潜在的法医临床益处。总之,这篇综述深入研究了CD8+T细胞的免疫动力学,微环境变化,和慢性HBV感染期间肝脏内的治疗策略,HCC进展,和相关的肝脏疾病。
Hepatitis B virus (HBV) infection playsa significant role in the etiology and progression of liver-relatedpathologies, encompassing chronic hepatitis, fibrosis, cirrhosis, and eventual hepatocellularcarcinoma (HCC). Notably, HBV infection stands as the primary etiologicalfactor driving the development of HCC. Given the significant contribution ofHBV infection to liver diseases, a comprehensive understanding of immunedynamics in the liver microenvironment, spanning chronic HBV infection,fibrosis, cirrhosis, and HCC, is essential. In this review, we focused on thefunctional alterations of CD8+ T cells within the pathogenic livermicroenvironment from HBV infection to HCC. We thoroughly reviewed the roles ofhypoxia, acidic pH, metabolic reprogramming, amino acid deficiency, inhibitory checkpointmolecules, immunosuppressive cytokines, and the gut-liver communication in shapingthe dysfunction of CD8+ T cells in the liver microenvironment. Thesefactors significantly impact the clinical prognosis. Furthermore, we comprehensivelyreviewed CD8+ T cell-based therapy strategies for liver diseases,encompassing HBV infection, fibrosis, cirrhosis, and HCC. Strategies includeimmune checkpoint blockades, metabolic T-cell targeting therapy, therapeuticT-cell vaccination, and adoptive transfer of genetically engineered CD8+ T cells, along with the combined usage of programmed cell death protein-1/programmeddeath ligand-1 (PD-1/PD-L1) inhibitors with mitochondria-targeted antioxidants.Given that targeting CD8+ T cells at various stages of hepatitis Bvirus-induced hepatocellular carcinoma (HBV + HCC) shows promise, we reviewedthe ongoing need for research to elucidate the complex interplay between CD8+ T cells and the liver microenvironment in the progression of HBV infection toHCC. We also discussed personalized treatment regimens, combining therapeuticstrategies and harnessing gut microbiota modulation, which holds potential forenhanced clinical benefits. In conclusion, this review delves into the immunedynamics of CD8+ T cells, microenvironment changes, and therapeuticstrategies within the liver during chronic HBV infection, HCC progression, andrelated liver diseases.