Yang Wuhan, Pan Teng, Chen Yaowen, Guo Hao, Peng Yaqi, Wang Chao, Peng Li, Wang Shubin
Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Oncology, Shijiazhuang First Hospital, Shijiazhuang, China.
Front Immunol. 2025 Jun 4;16:1576193. doi: 10.3389/fimmu.2025.1576193. eCollection 2025.
BACKGROUND: CD28PD-1 Tc cells (CD8 T cells) constitute a dysfunctional subset of T cell; however, the mechanisms underlying their dysfunction and their significance in hepatocellular carcinoma (HCC) remain unclear. We aimed to elucidate the prognostic significance and molecular characteristics of CD28PD-1 Tc cell infiltration in HCC. METHODS: We established a single-cell HCC transcriptional map, focusing on cell-cell communication and trajectory analysis of CD28PD-1 Tc cells. We assessed the correlation between CD28PD-1 Tc-cell enrichment and prognosis and investigated potential molecular mechanisms using enrichment analyses. Flow cytometry was used to compare CD28PD-1 Tc-cell infiltration between HCC and adjacent normal tissues and cytotoxic factors and immune checkpoint expression were evaluated. RESULTS: Overall, 25,644 T cells were identified from single-cell RNA sequencing data from 10 HCC samples and corresponding normal samples. Overall T-cell infiltration was lower in HCC tissues, with significantly higher CD28PD-1 Tc-cell infiltration. Bulk RNA sequencing data integration revealed a correlation between higher CD28PD-1 Tc-cell infiltration and significantly worse prognosis. Flow cytometry confirmed higher CD28PD-1 Tc-cell enrichment in HCC tissues. Additionally, cytotoxic factor expression was significantly lower in CD28PD-1 Tc cells than in CD28PD-1 Tc cells, with lower expression of TIGIT and TIM-3 immune checkpoint molecules. CONCLUSIONS: Significantly high CD28PD-1 Tc-cell enrichment in HCC indicates potential immune dysfunction. CD28PD-1 Tc-cell enrichment may serve as a sensitive prognostic marker and indicator for predicting treatment responses.
背景：CD28⁻PD-1⁺ Tc细胞（CD8⁺ T细胞）构成了功能失调的T细胞亚群；然而，其功能失调的潜在机制及其在肝细胞癌（HCC）中的意义仍不清楚。我们旨在阐明CD28⁻PD-1⁺ Tc细胞浸润在HCC中的预后意义和分子特征。 方法：我们建立了一个单细胞HCC转录图谱，重点关注CD28⁻PD-1⁺ Tc细胞的细胞间通讯和轨迹分析。我们评估了CD28⁻PD-1⁺ Tc细胞富集与预后之间的相关性，并使用富集分析研究潜在的分子机制。采用流式细胞术比较HCC与癌旁正常组织中CD28⁻PD-1⁺ Tc细胞的浸润情况，并评估细胞毒性因子和免疫检查点的表达。 结果：总体而言,从10例HCC样本和相应正常样本的单细胞RNA测序数据中鉴定出25644个T细胞。HCC组织中总的T细胞浸润较低，而CD28⁻PD-1⁺ Tc细胞浸润显著更高。批量RNA测序数据整合显示，较高的CD28⁻PD-1⁺ Tc细胞浸润与显著较差的预后相关。流式细胞术证实HCC组织中CD28⁻PD-1⁺ Tc细胞富集更高。此外，CD28⁻PD-1⁺ Tc细胞中的细胞毒性因子表达明显低于CD28⁺PD-1⁻ Tc细胞，TIGIT和TIM-3免疫检查点分子的表达也较低。 结论：HCC中显著高的CD28⁻PD-1⁺ Tc细胞富集表明潜在的免疫功能障碍。CD28⁻PD-1⁺ Tc细胞富集可能作为预测治疗反应的敏感预后标志物和指标。
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