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

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.

Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer

“…The role of the two TSLP isoforms has not been investigated in most of these studies. In addition, the commercial TSLP assay used in some studies ( 41 ) does not distinguish the two TSLP isoforms. The role of the two isoforms of TSLP in human cancers should be taken into account in future studies.…”

“…Using a variety of methods, several groups found that genetic rearrangements and mutations in the TSLP gene are present in pediatric acute lymphoblastic leukemia ( 165 – 167 ). TSLP is overexpressed in plasma and lymph nodes from Hodgkin patients ( 41 ). Moreover, TSLP acts through the production of Th2 cytokines (e.g., IL-4 and IL-13) to induce cutaneous T-cell lymphoma ( 168 ).…”

“…Interestingly, TSLP has now emerged as a cytokine with a plethora of pleiotropic properties mediated by the activation of a broad range of immune and non-immune cells. Depending on the immune cells targeted by TSLP, it is reported not only to promote Th2 response but also to be associated with autoimmune disorders ( 38 – 40 ) and cancer ( 32 , 34 , 41 ). Such a broad pathophysiological profile has motivated therapeutic targeting of TSLP- and TSLPR-mediated signaling ( 42 – 45 ).…”

Itching as a systemic disease

“…All of these cells are part of the tumor environment in patients with Hodgkin lymphoma and also implicated in those with pruritus. 29,[36][37][38] Cutaneous T-cell lymphoma (CTCL) is also accompanied by pruritus, and up to 88% of patients with CTCL complain of pruritus. Patients with advanced-stage CTCL have more severe itch than those with early-stage disease.…”

Development and identification of a fully human single‐chain variable fragment 29 against TSLP

“…Emerging evidences indicate that TSLP is also involved in chronic inflammatory, including chronic obstructive pulmonary disease, celiac disease, autoimmune disorders (e.g., psoriasis, rheumatoid arthritis), and several cancers. . These recent discoveries greatly expanded the understanding of the roles of TSLP in different human diseases, and such a broad pathophysiological profile has motivated the search for novel therapeutic options targeting TSLP‐ and TSLPR‐mediated signaling pathways .…”