Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome. Issue 8 (3rd July 2019)

• Record Type: Journal Article
• Authors: Anzengruber, Florian; Ignatova, Desislava; Schlaepfer, Tanja; Chang, Yun-Tsan; French, Lars E.; Pascolo, Steve; Contassot, Emmanuel; Bobrowicz, Malgorzata; Hoetzenecker, Wolfram; Guenova, Emmanuella
• Is Part Of: Leukemia & lymphoma. Volume 60:Issue 8(2019)
• Page Start: 1899
• Page End: 1907
• Publication Date: 2019-07-03
• Subjects: CTCL -- Sézary syndrome -- immune checkpoints -- immune exhaustion -- immunotherapy; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2018.1564827
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: 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; 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.