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.
Details
Download: 32760603_BIB_E73C64998C98.pdf (3479.85 [Ko])
State: Public
Version: Final published version
License: CC BY-NC 4.0
State: Public
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
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
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 11:03
Last modification date
15/01/2021 8:12