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.

Saulite, Ieva, Ignatova, Desislava, Chang, Yun-Tsan, Fassnacht, Christina, Dimitriou, Florentia, Varypataki, Eleni, Anzengruber, Florian, Nägeli, Mirjam, Cozzio, Antonio, Dummer, Reinhard, Scarisbrick, Julia, Pascolo, Steve, Hoetzenecker, Wolfram, Bobrowicz, Malgorzata and Guenova, Emmanuella (2020) 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. Oncoimmunology, 9 (1). p. 1738797. ISSN 2162-4011. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.

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Official URL: https://www.tandfonline.com/doi/full/10.1080/21624...

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 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.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.
Subjects: QZ Pathology. Oncology
WR Skin. Dermatology
Divisions: Ambulatory Care > Dermatology
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Depositing User: Mrs Noomi Tyholdt-Pidgley
Date Deposited: 29 Oct 2020 09:50
Last Modified: 29 Oct 2020 09:50
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3600

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