a Department of Dermatology , University Hospital Zurich University of Zurich , Zurich , Switzerland.
b Department of Immunology , Medical University of Warsaw , Warsaw , Poland.
Leuk Lymphoma. 2019 Aug;60(8):1899-1907. doi: 10.1080/10428194.2018.1564827. Epub 2019 Jan 14.
In Sézary syndrome (SS) impaired T-cell function and cytokine profile lead to immune evasion. Immune checkpoints non-redundantly regulate immune responses and targeting them is promising. We evaluated the expression of BTLA, CTLA-4, FCRL3, LAG-3, and TIGIT in tumor and non-tumor SS T-cells.Compared to CD4+ T helper cells from ten healthy individuals, tumor cells of eight SS patients had a significant upregulation of BTLA (1.5-fold; < .0001), FRCL3 (2.2-fold; < .0028) and TIGIT (2.2-fold; < .0003) expression. In contrast, we found a reduced expression of LAG-3+ cells in the blood of tumor patients (0.5-fold; < .0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; < .2022). Our results show a diverse expression pattern of immune-regulatory molecules in SS patients. As these molecules are essential in the regulation of T-cell mediated tumor surveillance and defense, their specific targeting might be of clinical relevance.
在赛扎里综合征（SS）中，T 细胞功能和细胞因子谱受损导致免疫逃逸。免疫检查点在调节免疫反应方面具有非冗余性，针对它们具有很大的应用前景。我们评估了 BTLA、CTLA-4、FCRL3、LAG-3 和 TIGIT 在肿瘤和非肿瘤 SS T 细胞中的表达。与来自 10 名健康个体的 CD4+辅助性 T 细胞相比，8 名 SS 患者的肿瘤细胞中 BTLA（1.5 倍；<0.0001）、FCRL3（2.2 倍；<0.0028）和 TIGIT（2.2 倍；<0.0003）的表达明显上调。相比之下，我们发现肿瘤患者血液中的 LAG-3+细胞表达减少（0.5 倍；<0.0014）。只有 CTLA-4 观察到肿瘤、非肿瘤细胞和健康对照之间的微弱改变（0.5 倍；<0.2022）。我们的研究结果显示 SS 患者中存在多种免疫调节分子的表达模式。由于这些分子在调节 T 细胞介导的肿瘤监视和防御中至关重要，因此针对它们的特定靶向治疗可能具有临床相关性。
