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

作者：Fengna Yan, Bingbing Zhu, Ke Shi, Yi Zhang, Xuanwei Zeng, Qun Zhang, Zhiyun Yang, Xianbo Wang · 发表于：Cancer Science · 年份：2024 · DOI：10.1111/cas.16247 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

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. The...