Biology and Clinical Applicability of Plasma Thymus and Activation-Regulated Chemokine (TARC) in Classical Hodgkin Lymphoma.

Marijn A Scheijde-Vermeulen,Christian M Zwaan,Arianne M Brandsma,Eline A M Zijtregtop,Iris Van Der Strate,Friederike Meyer-Wentrup,Auke Beishuizen

doi:10.3390/cancers13040884

Marijn A Scheijde-Vermeulen, Christian M Zwaan + Show 5 more

Open Access

https://doi.org/10.3390/cancers13040884

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Abstract

Simple SummaryThymus and activation-regulated chemokine (TARC) is an important biomarker in classical Hodgkin lymphoma and several other diseases. The exact role of TARC in the pathogenesis of these diseases, as well as its therapeutic potential, is not yet fully understood. Understanding the role of TARC in Hodgkin lymphoma is important since it might help in risk stratification of patients and it could be a therapeutic target. We give an overview of the biological functions of TARC and its potential as biomarker and therapeutic target.Thymus and activation-regulated chemokine (TARC) is produced by different cell types and is highly expressed in the thymus. It plays an important role in T cell development, trafficking and activation of mature T cells after binding to its receptor C-C chemokine receptor type 4 (CCR4) and consecutive signal transducer and activator of transcription 6 (STAT6) activation. Importantly, TARC is also produced by malignant Hodgkin and Reed–Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). In cHL, HRS cells survive and proliferate due to the micro-environment consisting primarily of type 2 T helper (Th2) cells. TARC-mediated signaling initiates a positive feedback loop that is crucial for the interaction between HRS and T cells. The clinical applicability of TARC is diverse. It is useful as diagnostic biomarker in both children and adults with cHL and in other Th2-driven diseases. In adult cHL patients, TARC is also a biomarker for treatment response and prognosis. Finally, blocking TARC signaling and thus inhibiting pathological Th2 cell recruitment could be a therapeutic strategy in cHL. In this review, we summarize the biological functions of TARC and focus on its role in cHL pathogenesis and as a biomarker for cHL and other diseases. We conclude by giving an outlook on putative therapeutic applications of antagonists and inhibitors of TARC-mediated signaling.

Highlights

Classical Hodgkin lymphoma is a malignancy of the lymphatic system with an incidence of 2–3/100,000 per year in developed countries [1]
We provide an overview of the use of Thymus and activation-regulated chemokine (TARC) as biomarker for oncological (Table 1) and nononcological (Table 2) diseases
TARC is a chemokine that is involved in different cellular pathways

Summary

Introduction

Classical Hodgkin lymphoma (cHL) is a malignancy of the lymphatic system with an incidence of 2–3/100,000 per year in developed countries [1]. Cell lines are rare and, in the absence of a microenvironment, only suitable for limited analysis of cellintrinsic properties, as they do not reflect the physiological situation of the lymphoma in vivo [17]. These characteristics of cHL have impeded the development of preclinical models to study the disease. More insight into the biology of the microenvironment will probably lead to additional improvements in treatment outcomes In light of this success, many studies have focused on associations of the tumor microenvironment and blood biomarkers with patient outcomes. We will review the role of TARC in cHL, its relevance as a marker of disease activity and its potential as a therapeutic target

Biology of TARC

Clinical Applicability of TARC

Findings

Conclusions