Evaluation of Sézary cell marker expression and cell death behaviour upon in vitro treatment by flow cytometry in Sézary syndrome patients
The diagnosis of Sézary syndrome (SS) relies on the identification of blood Sézary cells (SC) by different markers via flow cytometry. Treatment of SS is challenging since its pathogenesis is characterized by cell death resistance rather than hyperproliferation. In this study, we establish an integrated approach that considers both the expression of SC markers and sensitivity to cell death both spontaneously and upon in vitro treatment. Peripheral blood mononuclear cells were isolated from 20 SS patients and analysed for the SC markers CD7 and CD26 loss as well as CD158k and PD1 gain. The cells were then treated with different established and experimental therapies in vitro and cell death was measured. Spontaneous and therapeutically induced cell death were measured and correlated to cellular marker profiles. In the marker-positive cells, spontaneous cell death sensitivity was reduced. Different treatments in vitro managed to specifically induce cell death in the putative CTCL cell populations. Interestingly, a repeated analysis after 3 months of treatment revealed the CTCL cell death sensitivity to be restored by therapy. We propose this novel integrated approach comprising the evaluation of SC marker expression and analysis of cell death sensitivity upon treatment that can also enable a better therapy stratification.
Authors
- Rudolf Stadler (ORCID: https://orcid.org/0000-0003-2683-6028)
- Chalid Assaf (ORCID: https://orcid.org/0000-0002-7898-9432)
- Thomas Albrecht (ORCID: https://orcid.org/0000-0002-2234-0909)
- M. Roemer
- Jan P. Nicolay (ORCID: https://orcid.org/0000-0003-0220-0551)
- Marion Wobser (ORCID: https://orcid.org/0000-0002-6293-2554)
- Max Schlaak (ORCID: https://orcid.org/0000-0002-1663-8098)
- Rose K. C. Moritz (ORCID: https://orcid.org/0000-0001-7102-8762)
- Ulrike Wehkamp (ORCID: https://orcid.org/0000-0002-7398-4261)
- Susanne Melchers (ORCID: https://orcid.org/0000-0002-6456-2681)
- Emmanuella Guenova (ORCID: https://orcid.org/0000-0001-5478-8735)
- Sergij Goerdt (ORCID: https://orcid.org/0000-0002-5718-415X)
- John D. Albrecht (ORCID: https://orcid.org/0000-0001-7582-7051)
- Stefan W. Schneider (ORCID: https://orcid.org/0000-0002-4679-7137)
- C. von Gugelberg
- C.‐D. Klemke
Institutions
- University of Freiburg (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- Humboldt-Universität zu Berlin (DE)
- University Hospital of Zurich (CH)
- Helios Klinikum Krefeld (DE)
- München Klinik (DE)
- Universitätsklinikum Würzburg (DE)
- University Hospital in Halle (DE)
- University Medical Centre Mannheim (DE)
- Johannes Wesling Klinikum Minden (DE)
- Freie Universität Berlin (DE)
- University of Lausanne (CH)
Publication Details
- Journal
- Experimental Dermatology
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1111/exd.15171
- Citations
- 2
- Primary Topic
- Cutaneous lymphoproliferative disorders research
- Type
- article
- Field-Weighted Citation Impact
- 1.07
Funders
- National Science Foundation
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung