Background/Objectives: Liver and tumor-infiltrating T cells in hepatocellular carcinoma (HCC) are heterogeneous, comprising the CD69+tissue-resident T-cell and the CD69−circulating T-cell populations. However, the impact of these distinct T-cell populations on patient prognosis is unclear; hence, further studies are needed.Methods: Tumor and distant liver tissues from 57 HCC patients with various chronic liver disease etiologies were analyzed. Single-cell dissociation and flow cytometry were used to assess CD69+and CD69−T-cell populations and their correlation with recurrence-free survival (RFS).Results: CD69+/CD69−subpopulations within CD4+and CD8+T cells varied by patient and alcohol etiology. CD69−populations among CD4+T cells were less frequent in both tumor and non-tumor tissues of alcohol-related HCC patients (p< 0.05). Higher frequencies of CD69−CD4+and CD8+T cells in tumors and CD69+CD103+CD8+T cells in liver tissues were associated with better RFS. CD69- T cells expressed lower PD-1 levels, indicating less exhaustion, with PD-1 expression inversely correlated with CD69−frequency. PD-1 expression was higher in CD69−CD4+T cells in alcohol-related HCC.Conclusions: We provided a detailed analysis of the heterogeneous characteristics of tumor- and liver-infiltrating T cells in HCC, emphasizing the distinct roles of CD69+and CD69−cell populations and their impact on RFS. CD69+T cells were associated with immune exhaustion and tumor aggressiveness, whereas CD69−T cells appeared to significantly contribute to the influence of alcohol intake on the immune landscape of HCC in the tumor microenvironment. However, further research should validate these findings in larger cohorts to enhance our understanding.
背景/目的:肝细胞癌(HCC)中肝脏及肿瘤浸润T细胞具有异质性,包括CD69+组织驻留T细胞和CD69−循环T细胞群。然而,这些不同T细胞群对患者预后的影响尚不明确,因此需要进一步研究。 方法:本研究分析了57例不同慢性肝病病因的HCC患者的肿瘤组织及远端肝组织。采用单细胞解离和流式细胞术评估CD69+与CD69−T细胞群及其与无复发生存期(RFS)的相关性。 结果:CD4+和CD8+T细胞中的CD69+/CD69−亚群分布因患者及酒精病因存在差异。在酒精相关性HCC患者的肿瘤和非肿瘤组织中,CD4+T细胞中的CD69−群体出现频率较低(p<0.05)。肿瘤组织中较高频率的CD69−CD4+和CD8+T细胞,以及肝组织中较高频率的CD69+CD103+CD8+T细胞与更好的RFS相关。CD69−T细胞表达较低的PD-1水平,提示耗竭程度较轻,且PD-1表达与CD69−频率呈负相关。在酒精相关性HCC中,CD69−CD4+T细胞的PD-1表达更高。 结论:本研究详细分析了HCC中肿瘤及肝脏浸润T细胞的异质性特征,强调了CD69+与CD69−细胞群的不同作用及其对RFS的影响。CD69+T细胞与免疫耗竭和肿瘤侵袭性相关,而CD69−T细胞似乎在肿瘤微环境中对酒精摄入影响HCC免疫景观具有显著贡献。然而,仍需在更大规模队列中进一步验证这些发现以深化我们的理解。