Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sezary syndrome

In Sezary 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; p<.0001), FRCL3 (2.2-fold; p<.0028) and TIGIT (2.2-fold; p<.0003) expression. In contrast, we found a reduced expression of LAG-3+ cells in the blood of tumor patients (0.5-fold; p<.0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; p<.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.