Peng Lei, Liang Qi, Rong Peng Fei, Zhang Shengwang, Chen Huan, Liu Huaping, Ma Xiaoqian, Wang Wei
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
The Institute for Cell Transplantation and Gene Therapy, Central South University, Changsha, Hunan, China.
Therap Adv Gastroenterol. 2025 May 5;18:17562848251333295. doi: 10.1177/17562848251333295. eCollection 2025.
Although transcatheter arterial chemoembolization (TACE) is one of the first-line treatments for unresectable HCC (uHCC) patients, its overall efficacy varies significantly. Therefore, the identification of reliable biomarkers capable of effectively distinguishing TACE-responsive populations is clinically critical.
Our research aims to investigate T-lymphocyte subpopulations and associated pathways in peripheral blood that contribute to TACE refractoriness, as well as to develop effective methods for predicting TACE efficacy.
This is an observational study.
A total of 50 patients who underwent standard TACE-based therapy between January 2020 and December 2022 were included in this study. TACE response was evaluated within 1-3 months following two consecutive TACE sessions. Patients with TACE failure were assigned to the Non-Response group, whereas the remaining were categorized into the Response group. Blood samples were collected prior to treatment and subsequently analyzed using flow cytometry and RNA sequencing. Predictors were analyzed using univariate and multivariate analyses within the bivariate logistic regression models. Pathway enrichment analysis was performed using gene set enrichment analysis (GSEA).
A total of 24 of 50 (48%) exhibited TACE failure (Non-Response). Baseline peripheral T-lymphocyte analysis revealed that the Non-Response group had a higher abundance of senescent phenotype (T, CD27CD28) in both CD4/CD8 T cells ( < 0.0001), but a lower proportion of memory stem cell (T) subpopulation (CD4 T: p = 0.0411; CD8 T: < 0.0001). Furthermore, in CD8 T cells, they exhibited higher expression of exhaustion marks (PD-1: = 0.0005; LAG-3: = 0.0026; TIGIT: = 0.0014) and significantly lower production of effector molecules (TNF-α: < 0.0001; IFN-γ: = 0.0018; GZMB: < 0.0001). Transcriptomics revealed that the Response group was enriched in pathways associated with energy and drug metabolism. Univariate and multivariate analyses demonstrated that the baseline CD8 T and CD8 T subpopulations were significant predictive factors for TACE efficacy.
Our study demonstrated significant differences in the immune characteristics of peripheral T lymphocytes between the Non-Response and Response groups. The CD8 T and CD8 T subsets are potential predictors of TACE efficacy and long-term survival. These insights into peripheral blood T lymphocytes offer valuable evidence to help clinicians more effectively identify potential TACE-responsive populations, predict survival, and develop personalized treatment regimens for patients with uHCC.
尽管经动脉化疗栓塞术（TACE）是不可切除肝癌（uHCC）患者的一线治疗方法之一，但其总体疗效差异显著。因此，识别能够有效区分TACE反应人群的可靠生物标志物在临床上至关重要。
我们的研究旨在调查外周血中导致TACE难治性的T淋巴细胞亚群及相关通路，并开发预测TACE疗效的有效方法。
这是一项观察性研究。
本研究纳入了2020年1月至2022年12月期间接受标准TACE治疗的50例患者。在连续两次TACE治疗后的1-3个月内评估TACE反应。TACE治疗失败的患者被分配到无反应组，其余患者被分类为反应组。在治疗前采集血样，随后使用流式细胞术和RNA测序进行分析。在二元逻辑回归模型中使用单变量和多变量分析来分析预测因素。使用基因集富集分析（GSEA）进行通路富集分析。
50例患者中有24例（48%）出现TACE治疗失败（无反应）。基线外周T淋巴细胞分析显示，无反应组在CD4/CD8 T细胞中衰老表型（T，CD27CD28）的丰度较高（<0.0001），但记忆干细胞（T）亚群的比例较低（CD4 T：p = 0.0411；CD8 T：<0.0001）。此外，在CD8 T细胞中，它们表现出更高的耗竭标志物表达（PD-1：= 0.0005；LAG-3：= 0.0026；TIGIT：= 0.0014）以及效应分子的产生显著降低（TNF-α：<0.0001；IFN-γ：= 0.0018；GZMB：<0.0001）。转录组学显示，反应组在与能量和药物代谢相关的通路中富集。单变量和多变量分析表明，基线CD8 T和CD8 T亚群是TACE疗效的重要预测因素。
我们的研究表明，无反应组和反应组外周T淋巴细胞的免疫特征存在显著差异。CD8 T和CD8 T亚群是TACE疗效和长期生存的潜在预测指标。这些对外周血T淋巴细胞的见解提供了有价值的证据，有助于临床医生更有效地识别潜在的TACE反应人群、预测生存情况，并为uHCC患者制定个性化治疗方案。
