Abstract: The tumor microenvironment (TME) is the cornerstone and core of immunotherapy for hepatocellular carcinoma (HCC). HCC is highly heterogeneous, with significant differences in molecular pathological features between different etiologies and individuals. HCC lacks targetable driver genes and driver gene-guided targeted therapies, making TME an important entry point for integrating and classifying these diverse patients. Based on TME, HCC can be classified into inflammatory and non-inflammatory subtypes. Patients with inflammatory HCC can potentially benefit from monotherapy or combination therapy with immune checkpoint inhibitors (ICIs), while non-inflammatory patients require combination therapy with ICIs and angiogenesis inhibitors or tyrosine kinase inhibitors (TKIs) to enhance efficacy. Additionally, potential therapeutic strategies still in the experimental stage include targeting specific molecular pathways such as Wnt/β-catenin, and strategies to convert cold tumors into hot tumors by promoting T cell activation and expansion through immunoadjuvants, oncolytic viruses, tumor vaccines, radiotherapy, and chemotherapy. Adoptive cell therapies, especially chimeric antigen receptor T-cell (CAR-T) therapy, have shown great potential in the treatment of HCC. Furthermore, antibody-drug conjugates (ADCs) combined with immunotherapy and bispecific antibody therapies are promising new directions for future treatment development.

Key words: hepatocellular carcinoma, molecular characteristics, pathological characteristics, tumor microenvironment, immunotherapy

摘要： 肿瘤微环境（TME）是肝细胞癌（HCC）免疫综合治疗的基石和核心。HCC具有高度异质性，不同病因和个体之间的分子病理特征差异显著，HCC缺乏可靶向的驱动基因以及驱动基因指导的靶向治疗，而TME是对这些不同的病人进行整合分类的重要切入点。基于TME可将HCC分为炎症型和非炎症型两大类，炎症型HCC病人可从免疫检查点抑制剂（ICIs）单药或联合治疗中获益，而非炎症型病人则需要ICIs与血管生成抑制剂或酪氨酸激酶抑制剂（TKIs）等的联合治疗以提高疗效。此外，尚处实验阶段的潜在治疗策略，包括靶向特定分子通路如Wnt/β-catenin的治疗，以及将冷肿瘤转化为热肿瘤的策略，如通过免疫佐剂、溶瘤病毒、肿瘤疫苗、放疗和化疗等方法促进T细胞的活化和扩增，未来将进一步助力HCC免疫治疗。过继细胞疗法，尤其是嵌合抗原受体T细胞（CAR-T）疗法，在HCC中展现了出巨大潜力，抗体药物偶联物（ADCs）联合免疫治疗以及双特异性抗体疗法也是未来有潜力的新方向，这些综合策略必将扩大免疫治疗的可及性和有效性。

关键词: 肝细胞癌, 分子特征, 病理学特征, 肿瘤微环境, 免疫治疗