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
Saulite, Ieva
Ignatova, Desislava
Chang, Yun-Tsan
Fassnacht, Christina
Dimitriou, Florentia
Varypataki, Eleni
Anzengruber, Florian
Nägeli, Mirjam
Cozzio, Antonio
Dummer, Reinhard
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Affiliation
University Hospital Zurich; University of Zurich; Cantonal Hospital St. Gallen; University Hospitals Birmingham NHS Foundation Trust; Kepler University Hospital; Medical University of Warsaw; Lausanne University Hospital CHUV; University of Lausanne
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2020-03-18
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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.
Citation
Saulite I, Ignatova D, Chang YT, Fassnacht C, Dimitriou F, Varypataki E, Anzengruber F, Nägeli M, Cozzio A, Dummer R, Scarisbrick J, Pascolo S, Hoetzenecker W, Bobrowicz M, Guenova E. 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. 2020 Mar 18;9(1):1738797. doi: 10.1080/2162402X.2020.1738797.
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Article