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. 2023 Oct 25;189(5):603-611.
doi: 10.1093/bjd/ljad220.

Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in patients with leukaemic cutaneous T-cell lymphoma

Yi-Chien Tsai  1 , Tanja Schlaepfer  2 , Desislava Ignatova  2 , Yun-Tsan Chang  1 , Alan Valaperti  3 , Boyko Amarov  4 , Gabriela Blanchard  1 , Kevin Pehr  5 , Maya Vonow-Eisenring  3 , Mirjana Urosevic-Maiwald  6 , Wolfram Hoetzenecker  7 , Steve Pascolo  2 , Christoph Iselin  1 , Christina Fassnacht  2 , Florentia Dimitriou  2 , Malgorzata Bobrowicz  8 , Emmanuella Guenova  1   2
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Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in patients with leukaemic cutaneous T-cell lymphoma

Yi-Chien Tsai et al. Br J Dermatol. .

Erratum in

  • Correction.
    [No authors listed] [No authors listed] Br J Dermatol. 2024 Jun 20;191(1):e1. doi: 10.1093/bjd/ljae157. Br J Dermatol. 2024. PMID: 38709154 No abstract available.

Abstract

Background: Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30 years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce.

Objectives: We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action.

Methods: A total of 25 patients with L-CTCL and 15 healthy donors (HDs) were enrolled in this retrospective cohort study. Concentrations of 22 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. Neoplastic cells in patients' blood were evaluated by flow cytometry.

Results: Firstly, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of tumour necrosis factor (TNF)-α, and significant increase of interleukins (IL)-9, IL-12 and IL-13 in the sera of patients with L-CTCL compared with HDs. Secondly, patients with L-CTCL who received ECP were classified as treatment responders and nonresponders according to the quantitative reduction of malignant burden in their blood. We evaluated cytokine levels in culture supernatants from patients' peripheral blood mononuclear cells (PBMCs) at baseline and 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α in comparison with ECP nonresponders. In parallel, responders showed clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immune cytokines in individual patients with L-CTCL.

Conclusions: Taken together, our results demonstrate that ECP stimulates the innate immune network, and facilitates redirection of the tumour-biased immunosuppressive microenvironment towards proactive antitumour immune responses. The alterations of IL-1α, IL-1β, GM-CSF and TNF-α can be used as biomarkers of response to ECP in patients with L-CTCL.

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Conflict of interest statement

Conflicts of interest: F.D. has received honoraria and travel support from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Sun Pharma. E.G. has received consulting fees, payment or honoraria and/or research grant support from Helsinn, KIOWA Kirin, Mallinckrodt Pharmaceuticals, Novartis, Recordati Rare Diseases, Sanofi and Takeda outside the scope of the submitted work, has a patent on a diagnostic method for blood disease, has been involved in a leadership role for the European Academy of Dermatology and Venereology and European Organization for Research and Treatment of Cancer, and has stock/stock options for Scailyte AG.

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