Interleukin-31 and thymic stromal lymphopoietin expression in plasma and lymph node from Hodgkin lymphoma patients

// Elisa Ferretti 1, * , Stefan Hohaus 2, * , Arianna Di Napoli 3 , Beatrice Belmonte 4 , Annarosa Cuccaro 2 , Elisa Cupelli 2 , Eugenio Galli 2 , Vittoria Rufini 5 , Gino Tripodi 6 , Giulio Fraternali-Orcioni 7 , Vito Pistoia 8, * and Anna Corcione 1, * 1 Laboratory of Oncology, Istituto Giannina Gaslini, Genova, Italy 2 Institute of Hematology, Catholic University of the Sacred Heart, Roma, Italy 3 Department of Clinical and Molecular Medicine, Pathology Unit, Sant'Andrea Hospital, Sapienza University, Roma, Italy 4 Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo, Palermo, Italy 5 Institute of Nuclear Medicine, Catholic University of the Sacred Heart, Roma, Italy 6 Immunohaematology and Transfusion Centre, Istituto Giannina Gaslini, Genova, Italy 7 Unit of Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino – IST – Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy 8 Immunology Research Area, Ospedale Pediatrico Bambino Gesu, Roma, Italy * These authors have contributed equally to this work Correspondence to: Anna Corcione, email: annacorcione@ospedale-gaslini.ge.it Keywords: Hodgkin lymphoma, IL-31, TSLP, cytokine receptors, PET Received: December 20, 2016      Accepted: May 21, 2017      Published: July 28, 2017 ABSTRACT Hodgkin Lymphoma (HL) is a tumor of B-cell origin characterized by Hodgkin and Reed-Stenberg (H/RS) cells embedded in an inflammatory tissue where numerous cytokines/chemokines contribute to shape the microenvironment, leading to the typical clinical symptoms. We investigated: i) the expression of Interleukin-IL-31 (IL-31) and Thymic Stromal Lymphopoietin (TSLP), two Th2-related cytokines with tumor-promoting and pruritogenic functions, and of the respective receptors in HL invaded lymph nodes by flow cytometry, and ii) the potential association of IL-31/TSLP plasma concentrations with clinical characteristics by ELISA. H/RS cells and the major immune cell types infiltrating HL lymph nodes expressed intracytoplasmic and surface IL-31/TSLP, and their receptors. A subgroup of patients showing at diagnosis elevated IL-31 and TSLP plasma levels had an International Prognostic Score>2, indicative of high risk of relapse, and a subsequent positive interim PET-scan, indicative of insufficient response to chemotherapy. No correlation was found between IL-31/TSLP plasma levels and overall or event-free survival. In conclusion, IL-31/TSLP and their receptors are expressed in HL cells and in immune cells infiltrating affected lymph nodes, where both cytokines may contribute to local immune suppression. The clinical impact of IL-31 and TSLP plasma levels has to be further defined in larger patient cohorts.