Journal Article

Prognostic and therapeutic potential of imbalance between PD‐1+CD8 and ICOS+Treg cells in advanced HBV‐HCC

Zhu, Bingbing, Zhang, Qun, Yang, Zhiyun, Zhang, Yi, Yan, Fengna, Shi, Ke, Wang, Xianbo, Zeng, Xuanwei

2024

Overview

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. Imbalance between CD8+ T cells and regulatory T (Treg) cells accelerates disease progression, but there is no imbalance indicator to predict clinical outcomes. The ratio between PD‐1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced hepatitis B virus‐associated hepatocellular carcinoma (HBV‐HCC).

• Publisher: John Wiley & Sons, Inc
• Subject: Antigens / Apoptosis / CD8 antigen / Cell proliferation / Clinical outcomes / Flow cytometry / Hepatitis B / hepatitis B virus‐associated hepatocellular carcinoma / Hepatocellular carcinoma / ICOS+Tregs / Immune checkpoint inhibitors / immune imbalance / Immunological memory / Immunotherapy / Liver cancer / Lymphocytes / Lymphocytes T / Medical prognosis / Memory cells / PD‐1+CD8 cells / Prognosis / tumor progression / Viral infections