Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan; National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2021 Aug;120(8):1581-1590. doi: 10.1016/j.jfma.2020.11.015. Epub 2020 Dec 15.
BACKGROUND/PURPOSE: Recent progress in cancer immunology provides more insight in immune evasion of cancer cells. Cancer cells may achieve immune evasion through several ways including ineffective antigen presentation, T cell checkpoint utilization, immunosuppressive cytokines secretion and immunosuppressive cells recruitment. However, few literatures mentioned about the change of peripheral blood immune cells in advanced hepatocellular carcinoma (HCC) patients. To answer this question, we initiated a pilot study through detailed flow cytometry.
We enrolled patients with advanced HCC patients who had informed consent to the collection of their peripheral blood. We also recruited healthy individuals for the control group. Using flow cytometry, we analyzed lymphocyte subclasses and the PD-1 or PD-L1 positivity of immune cells in peripheral blood from HCC patients and healthy individuals.
Twenty-four HCC patients were enrolled and twenty healthy individuals were enrolled. Most of the HCC patients were HBV carrier (58.3%), and the mean age was 61 years old. Among 55 immune cell parameters we examined in peripheral blood, 16 were significantly different between advanced HCC patients and healthy individuals by univariate analysis. Multivariate analysis was then conducted by fitting logistic regression model and showed that CD69CD25 Naïve CD4αβT cell percentage and dendritic cell percentage can reasonably predict the advanced HCC status from peripheral blood. By our regression model, the adjusted generalized R2 = 0.918 and the estimated area under the Receiver Operating Characteristic (ROC) curve was 0.99.
CD69CD25 Naïve CD4αβT cell percentage and dendritic cell percentage in peripheral blood are highly correlated with the advanced HCC status. The change may result from immune evasion initiated by hepatocellular carcinoma cells and further investigation is warranted. Validation study is ongoing and this mechanism may be utilized to treat advanced HCC patient in the future.
背景/目的：癌症免疫学的最新进展为了解癌细胞的免疫逃逸机制提供了更多的线索。癌细胞可能通过多种途径实现免疫逃逸，包括抗原呈递无效、T 细胞检查点利用、免疫抑制细胞因子分泌和免疫抑制细胞募集。然而，很少有文献提到晚期肝细胞癌（HCC）患者外周血免疫细胞的变化。为了回答这个问题，我们通过详细的流式细胞术启动了一项初步研究。
我们招募了已签署知情同意书同意收集外周血的晚期 HCC 患者。我们还招募了健康个体作为对照组。我们使用流式细胞术分析了 HCC 患者和健康个体外周血中的淋巴细胞亚群和免疫细胞的 PD-1 或 PD-L1 阳性率。
共纳入 24 例 HCC 患者和 20 名健康个体。大多数 HCC 患者为 HBV 携带者（58.3%），平均年龄为 61 岁。在我们检查的外周血 55 个免疫细胞参数中，16 个参数通过单变量分析在晚期 HCC 患者和健康个体之间存在显著差异。然后通过拟合逻辑回归模型进行多变量分析，结果显示 CD69CD25 Naïve CD4αβT 细胞百分比和树突状细胞百分比可以合理地从外周血预测晚期 HCC 状态。通过我们的回归模型，调整后的广义 R2 为 0.918，ROC 曲线下面积估计值为 0.99。
外周血中 CD69CD25 Naïve CD4αβT 细胞百分比和树突状细胞百分比与晚期 HCC 状态高度相关。这种变化可能是由肝癌细胞启动的免疫逃逸引起的，需要进一步研究。验证研究正在进行中，该机制可能用于未来治疗晚期 HCC 患者。
