Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally, driven by chronic liver disease and a complex tumor microenvironment (TME). Recent advances in spatial omics, single-cell analyses, and AI-driven digital pathology have shed light on the intricate heterogeneity of HCC, highlighting key roles for immune suppression, angiogenesis, and fibrosis in tumor progression. This review synthesizes current epidemiological trends, noting a shift from viral hepatitis to metabolic syndrome as a primary etiology in Western populations, and elucidates how TME components—such as tumor-associated macrophages, cancer-associated fibroblasts, vascular endothelial cells, and immunosuppressive cytokines—contribute to resistance against conventional therapies. We detail the evolution of immunotherapeutic strategies from monotherapy to combination regimens, including dual immune checkpoint blockade and the integration of antiangiogenic agents. Emerging circulating and tissue-based biomarkers offer promise for enhanced patient stratification and real-time monitoring of treatment responses. Collectively, these innovations herald a paradigm shift toward TME-directed precision oncology in HCC, emphasizing the need for multi-targeted approaches to synergistically modulate interacting cellular constituents and ultimately improve clinical outcomes.
肝细胞癌（HCC）作为全球致死率最高的恶性肿瘤之一，其发生发展主要受慢性肝病及复杂肿瘤微环境驱动。近年来，空间组学、单细胞分析及人工智能驱动的数字病理学进展揭示了HCC的高度异质性，凸显了免疫抑制、血管生成和纤维化在肿瘤演进中的关键作用。本综述整合当前流行病学趋势，指出西方人群主要病因已从病毒性肝炎转向代谢综合征，并系统阐释了肿瘤相关巨噬细胞、癌症相关成纤维细胞、血管内皮细胞及免疫抑制性细胞因子等肿瘤微环境组分如何导致传统治疗耐药。我们详细梳理了从单药治疗到联合方案的免疫治疗策略演进，包括双免疫检查点阻断及抗血管生成药物的整合应用。新兴的循环与组织生物标志物为优化患者分层及实时监测治疗反应提供了新方向。这些创新成果共同预示着HCC治疗范式正朝着肿瘤微环境导向的精准肿瘤学转变，强调需要通过多靶点策略协同调控相互作用的细胞成分，最终改善临床预后。
肿瘤(癌症)患者之家