Titre
Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in patients with leukaemic cutaneous T-cell lymphoma.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Tsai, Y.C.
Auteure/Auteur
Schlaepfer, T.
Auteure/Auteur
Ignatova, D.
Auteure/Auteur
Chang, Y.T.
Auteure/Auteur
Valaperti, A.
Auteure/Auteur
Amarov, B.
Auteure/Auteur
Blanchard, G.
Auteure/Auteur
Pehr, K.
Auteure/Auteur
Vonow-Eisenring, M.
Auteure/Auteur
Urosevic-Maiwald, M.
Auteure/Auteur
Hoetzenecker, W.
Auteure/Auteur
Pascolo, S.
Auteure/Auteur
Iselin, C.
Auteure/Auteur
Fassnacht, C.
Auteure/Auteur
Dimitriou, F.
Auteure/Auteur
Bobrowicz, M.
Auteure/Auteur
Guenova, E.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1365-2133
Statut éditorial
Publié
Date de publication
2023-10-25
Volume
189
Numéro
5
Première page
603
Dernière page/numéro d’article
611
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
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.
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.
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.
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.
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.
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.
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.
PID Serval
serval:BIB_ACBD06166FA1
PMID
Open Access
Oui
Date de création
2023-07-10T12:29:15.195Z
Date de création dans IRIS
2025-05-20T22:15:50Z
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Nom
37409661.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.64 MB
Format
Adobe PDF
PID Serval
serval:BIB_ACBD06166FA1.P001
URN
urn:nbn:ch:serval-BIB_ACBD06166FA18
Somme de contrôle
(MD5):27fe172212cfd00e317d5a7434b7b9fb