Background
Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and 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 L-CTCL patients 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 patient blood were evaluated by flow cytometry.
Results
First, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of TNFα, and significant increase of IL-9, IL-12 and IL-13 in the sera of L-CTCL patients compared to HDs. Second, L-CTCL patients who received ECP were classified as treatment responders and non-responders according to their quantitative reduction of malignant burden in the blood. We evaluated cytokine levels in culture supernatants from patient peripheral blood mononuclear cells (PBMCs) at baseline and after 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1β, GM-CSF and TNF-α in comparison with ECP non-responders. 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 L-CTCL patients.
Conclusions
Taken together, our results demonstrate that ECP stimulates innate immune network, and facilitates redirection of tumour-biased immunosuppressive microenvironment towards proactive anti-tumour immune responses. The alterations of IL-1α, IL-1β, GM-CSF and TNF-α can be used as biomarkers of response to ECP in L-CTCL patients.