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

Cancer Immunol Immunother. 2025 Jul 1;74(8):257. doi: 10.1007/s00262-025-04122-z.

Abstract

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.

Keywords: Adoptive cellular therapy; Cellular immunotherapy; Hepatitis B virus (HBV); Hepatocellular carcinoma; T-cell; T-cell receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / therapy
  • Humans
  • Immunotherapy / methods
  • Immunotherapy, Adoptive* / methods
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / therapy
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • T-Lymphocytes* / immunology

Substances

  • Receptors, Antigen, T-Cell