Prognostic and therapeutic potential of imbalance between <scp>PD</scp>‐1+<scp>CD8</scp> and <scp>ICOS</scp>+Treg cells in advanced <scp>HBV</scp>‐<scp>HCC</scp>
Fengna Yan, Bingbing Zhu, Ke Shi, Yi Zhang, Xuanwei Zeng, Qun Zhang, Zhiyun Yang, Xianbo Wang
Abstract
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/ICOS hi ) and low‐ratio (PD‐1/ICOS lo ) groups according to ratio median. Compared with PD‐1/ICOS lo patients, the PD‐1/ICOS hi 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/ICOS hi patients exhibited a higher proportion of tissue‐resident memory T (T RM ) cells and had more stable killing capacity and lower apoptosis capacity than PD‐1/ICOS lo 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.