Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, with the majority of cases detected at advanced stages when curative options are limited. Current systemic therapies, including immune checkpoint inhibitors, demonstrate limited efficacy with durable responses in only 15–20% of patients. This poor response is largely attributed to HCC’s immunosuppressive microenvironment, which blunts effective T-cell responses. By illustrating that innate immune cells can acquire memory-like characteristics through a process known as trained immunity, recent evidence has challenged the conventional belief that innate immunity is devoid of memory. This review investigates the potential of trained immunity, which is defined by the long-term functional reprogramming of innate immune cells through epigenetic, transcriptomic, and metabolic changes, to provide new therapeutic opportunities for HCC. We discuss mechanisms by which trained immunity can transform the HCC microenvironment, including enhanced inflammatory cytokine production, repolarization of tumor-associated macrophages toward anti-tumor phenotypes, increased immune cell infiltration, and improved bridging to adaptive immunity. We further evaluate emerging therapeutic strategies leveraging trained immunity principles, including BCG vaccination, β-glucan administration, cytokine-trained NK cell therapy, and innovative combination approaches. Finally, we address potential resistance mechanisms and future directions for clinical application. By integrating trained immunity into conventional immunotherapeutic regimens, we may significantly improve outcomes for HCC patients, potentially transforming advanced disease into a more manageable condition.
肝细胞癌是全球癌症死亡的主要原因，多数病例确诊时已至晚期，根治性治疗手段有限。当前包括免疫检查点抑制剂在内的全身性治疗方案疗效有限，仅15%-20%患者能获得持久应答。这种治疗反应不佳主要归因于肝细胞癌的免疫抑制微环境，该环境会削弱有效的T细胞应答。近期研究通过揭示先天免疫细胞可通过"训练免疫"过程获得类记忆特性，挑战了传统认为先天免疫缺乏记忆功能的观点。本综述探讨训练免疫——即通过表观遗传、转录组和代谢变化实现先天免疫细胞长期功能重编程——为肝细胞癌提供新治疗机遇的潜力。我们系统阐述训练免疫改造肝细胞癌微环境的作用机制，包括增强炎性细胞因子产生、促使肿瘤相关巨噬细胞向抗肿瘤表型复极化、增加免疫细胞浸润以及强化与适应性免疫的衔接。进一步评估基于训练免疫原理的新兴治疗策略，包括卡介苗接种、β-葡聚糖给药、细胞因子训练的自然杀伤细胞疗法及创新联合治疗方案。最后探讨潜在的耐药机制及临床应用前景。通过将训练免疫整合至常规免疫治疗方案，有望显著改善肝细胞癌患者预后，或将晚期疾病转化为更可控状态。
肿瘤(癌症)患者之家