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Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation
- Source :
- OncoImmunology, Vol 9, Iss 1 (2020)
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis Group, 2020.
-
Abstract
- Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4+ T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4+ T cells from SS patients and to CD4+ cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor.
Details
- Language :
- English
- ISSN :
- 2162402X
- Volume :
- 9
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.39901325e57947a4b3306900403a79ac
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/2162402X.2020.1738797