ABSTRACT
Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.
Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular , Inducible T-Cell Co-Stimulator Protein , Liver Neoplasms , Programmed Cell Death 1 Receptor , T-Lymphocytes, Regulatory , Humans , Programmed Cell Death 1 Receptor/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Inducible T-Cell Co-Stimulator Protein/metabolism , Prognosis , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Male , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/virology , Liver Neoplasms/metabolism , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/metabolism , Female , Middle Aged , Hepatitis B virus/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Adult , Aged , Hepatitis B/immunologyABSTRACT
The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387-0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.