Bio-P-13 - Boost of innate immunity cytokines as biomarkers of response to extracorporeal photopheresis in leukemic cutaneous T-cell lymphoma patients

Abstract

Extracorporeal photopheresis (ECP) emerged as a systemic first-line therapy in leukemic cutaneous T-cell lymphoma (L-CTCL) and is now being implemented in a variety of T-cell-mediated diseases. Although ECP has been used for nearly 30 years, the mechanisms of its efficacy are not sufficiently understood and biomarkers for response are lacking. We aim to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL. A total of 22 L-CTCL patients and 15 healthy donors (HDs) were retrospectively enrolled in this study. Concentrations of 16 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. First, the result revealed distinct cytokine patterns between L-CTCLs and HDs. We observed significant loss of TNFa and IL-8, and significant increase of IL-9 and IL-13 in serums of L-CTCL patients compare to HDs. As a next step, L-CTCL patients who received ECP were classified to responder and non-responder to treatment 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 over 27 weeks after ECP. Strikingly, PBMCs purified from ECP responders released statistically higher concentration of innate immunity cytokines such as IL-1a, IL-1b, GM-CSF and TNFα in comparison with ECP non-responders. In parallel, clinical observations documented complete clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immunity cytokines in individual L-CTCL patients. To conclude, our results demonstrated that ECP stimulates innate immune network, and this implied how ECP facilitates redirection of tumor-biased immunosuppressive microenvironment toward active anti-tumor responses. The alteration of TNFα, IL-1a, IL-1b and GM-CSF can possibly be used as biomarkers of response to ECP in leukemic CTCL patients.