Chai Yinying, Xu Tinghui, Chen Xin, Chen Bihua, Du Xinghai, Zhang Zhezhong
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2025 Jun 11;16:1621243. doi: 10.3389/fimmu.2025.1621243. eCollection 2025.
Liver cancer is a major global health burden, with hepatocellular carcinoma (HCC) being the most common type. Liver cancer tumor-initiating cells (TICs) are responsible for recurrence, metastasis, and therapeutic resistance, thereby presenting formidable treatment challenges. This review provides a comprehensive summary of the biological features of liver cancer TICs, including their potential cellular origins, diagnostic difficulties, key signaling pathways, and complex interactions with the tumor immune microenvironment. Special emphasis is placed on immunotherapeutic strategies, which have shown notable progress but remain limited by TIC-induced immune resistance. The review discusses current approaches such as immune checkpoint inhibitors (ICIs), adoptive cell therapies, and tumor vaccines, as well as combination strategies integrating immunotherapy with chemotherapy, targeted therapy, and locoregional interventions. Furthermore, emerging strategies including gene editing, targeted tyrosine kinase inhibition, and artificial intelligence-based tumor prediction are being explored for their potential to improve therapeutic efficacy. The significance of this review lies in highlighting the importance of surmounting the challenges presented by TICs to boost the efficacy of liver cancer treatment. In conclusion, although existing treatment approaches have demonstrated promise, further research is warranted to elucidate the origins of TICs, establish accurate diagnostic methods, and overcome resistance, ultimately enhancing the efficacy of liver cancer treatment and improving patient outcomes.
肝癌是一项重大的全球健康负担，肝细胞癌（HCC）是最常见的类型。肝癌肿瘤起始细胞（TIC）导致复发、转移和治疗抗性，从而带来严峻的治疗挑战。本综述全面总结了肝癌TIC的生物学特征，包括其潜在的细胞起源、诊断困难、关键信号通路以及与肿瘤免疫微环境的复杂相互作用。特别强调了免疫治疗策略，这些策略已显示出显著进展，但仍受TIC诱导的免疫抗性限制。该综述讨论了当前的方法，如免疫检查点抑制剂（ICI）、过继性细胞疗法和肿瘤疫苗，以及将免疫疗法与化疗、靶向治疗和局部区域干预相结合的联合策略。此外，正在探索包括基因编辑、靶向酪氨酸激酶抑制和基于人工智能的肿瘤预测在内的新兴策略，以提高治疗效果。本综述的意义在于强调克服TIC带来的挑战对提高肝癌治疗效果的重要性。总之，尽管现有治疗方法已显示出前景，但仍需进一步研究以阐明TIC的起源、建立准确的诊断方法并克服抗性，最终提高肝癌治疗效果并改善患者预后。
