TCR-based cellular immunotherapy for hepatocellular carcinoma: advances, challenges, and prospects

• Published in: Cancer Immunology, Immunotherapy : CII Vol. 74; no. 8; pp. 257 - 21
• Main Authors: Zeng, Wanting, Zhu, Wei, Yuan, Guosheng, Chen, Jinzhang, Wang, Zhanhui, Hou, Jinlin, Jiang, De-Ke
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2025; Springer Nature B.V; Springer
• Subjects: Ablation; Adoptive cellular therapy; Animals; Antigens; Cancer Research; Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - therapy; Cell therapy; Cellular immunotherapy; Chemoembolization; Clinical medicine; Clinical trials; Epidemiology; Hepatitis B; Hepatitis B virus (HBV); Hepatocellular carcinoma; Humans; Immunology; Immunotherapy; Immunotherapy - methods; Immunotherapy, Adoptive - methods; Kinases; Liver cancer; Liver Neoplasms - epidemiology; Liver Neoplasms - immunology; Liver Neoplasms - therapy; Lymphocytes; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Mortality; Oncology; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Review; T cell receptors; T-cell; T-cell receptor; T-Lymphocytes - immunology; Transplants & implants; Tumors; Asia; China; T-cell receptor; Hepatocellular carcinoma; Cellular immunotherapy; T-cell; Hepatitis B virus (HBV); Adoptive cellular therapy
• ISSN: 1432-0851; 0340-7004; 1432-0851
• DOI: 10.1007/s00262-025-04122-z

Hepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumors globally. However, current frontline treatment modalities fail to achieve satisfactory therapeutic outcomes. In recent years, T-cell receptor (TCR)-T therapy has garnered increasing attention as a promising therapeutic approach. This review provides an overview of the epidemiology of HCC, evaluates the efficacy of current first-line treatment options, and introduces adoptive cellular therapies (ACTs), with a specific focus on TCR-T therapy. Notably, we categorize existing TCR-T research targeting different antigens for the treatment of HCC, covering both published literature and registered clinical trials. Furthermore, we discuss the limitations of current TCR-T research and applications, while offering insights into future research directions and development prospects. In summary, this review comprehensively examines the research progress on TCR-T therapy for HCC from the perspective of antigen targeting. Although several challenges remain to be addressed, we believe that TCR-T therapy represents a promising approach for the treatment of HCC.