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.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_E73C64998C98
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Oncoimmunology
Author(s)
Saulite I., Ignatova D., Chang Y.T., Fassnacht C., Dimitriou F., Varypataki E., Anzengruber F., Nägeli M., Cozzio A., Dummer R., Scarisbrick J., Pascolo S., Hoetzenecker W., Bobrowicz M., Guenova E.
ISSN
2162-4011 (Print)
ISSN-L
2162-4011
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
9
Number
1
Pages
1738797
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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 <sup>+</sup> 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 <sup>+</sup> T cells from SS patients and to CD4 <sup>+</sup> 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.
Keywords
Monoclonal antibody, PD-1, PD-L1, PD-L2, Sézary Syndrome, immunotherapy, leukemic cutaneous T-cell lymphoma
Pubmed
Web of science
Open Access
Yes
Create date
17/08/2020 10:03
Last modification date
15/01/2021 7:12
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