Journal Article

DKFZ-2026-01761

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Malignant T Cells Operate at the Edge of Redox Tolerance and Propagate Oxidative Stress in Cutaneous T-Cell Lymphoma.

Namini, M. R. J. ; Nielsen, P. R. ; Gluud, M. ; Yan, L. ; Vadivel, C. K. ; Zeng, Z. ; Hasselager, S. S. ; Willerslev-Olsen, A. ; Ahmad, S. ; Sorrosal, L. P. ; Geisler, C. ; Bonefeld, C. M. ; Woetmann, A. ; Wang, C. K. ; Gyrd-Hansen, M. ; Assaf, C. ; Becker, J. C.DKFZ* ; Litman, T. ; Bzorek, M. ; Gjerdrum, L. R. ; Lilla, S. ; Zanivan, S. ; Krejsgaard, T. ; Buus, T. B. ; Ødum, N.

2026
Elsevier Amsterdam

Abstract: Reactive oxygen species (ROS) are tightly regulated in the skin and implicated in both cancer and inflammatory dermatoses, but the role of oxidative stress in cutaneous T-cell lymphoma (CTCL) remains largely unexplored. Here we aim to characterize oxidative stress and redox homeostasis in CTCL and determine whether increased ROS creates a therapeutic vulnerability in malignant T-cells and whether it affects neighboring keratinocytes. Lesional MF skin display increased oxidative DNA- and lipid-membrane- damage and a redox gene signature distinct from atopic dermatitis, characterized by SOD2 overexpression and PRDX2 repression - a rare redox profile confirmed at protein level. Primary malignant T-cells show widespread cysteine oxidation and constitutively elevated intracellular and mitochondrial ROS. Malignant T-cells are selectively killed by DMNQ (and rescued by NAC) demonstrating they operate near their maximal antioxidant capacity. Romidepsin-induced apoptosis is similarly NAC-dependent. Supernatants from malignant (but not non-malignant) T-cells induce elevated ROS and recapitulate the SOD2-high/PRDX2-low signature in keratinocytes. This effect is amplified by S. aureus activation. Taken together, we find that CTCL harbors a rare SOD2-high/PRDX2-low redox imbalance and that malignant T-cells are sensitive to ROS induction while able to propagate oxidative stress to keratinocytes.

Keyword(s): Oxidative Stress ; Reactive Oxygen Species ; Staphylococcus Aureus ; cutaneous T cell lymphoma ; skin barrier

Note: #DKTKZFB26# / epub

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
2. DKTK ED Translationale Hautkrebsforschung (ED03)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---