Chemokines and antagonists in non-Hodgkin's lymphoma

Abstract

Background: Chemokines and their receptors are a large family of molecules that control the trafficking of immune cells during their development and in response to inflammation. Non Hodgkin's lymphoma (NHL) derives from the neoplastic transformation of lymphocytes at different stages of differentiation and may show systemic, nodal and extranodal localisation as well as metastasis in different sites. Objective: To investigate the role of the chemokine system in the pathology of NHL and as a potential drug target in this disease. Method: The expression of chemokines and receptors by different NHL subtypes as well as their likely functional role in terms of lymphoma tissue localisation, lymphoma growth, tumour angiogenesis and recruitment of immune cells are reviewed. The data regarding antagonists or chemokines as potential therapeutic agents for NHL is discussed. Results/conclusions: NHL's express functional chemokine receptors, which, at least in part, dictate tissue localisation and perhaps metastatic potential. Different types of chemokine antagonists have been tested in vitro and in vivo and several peptide or small molecule inhibitors have reached Phase I/II clinical trials for different diseases. Although the field is in its early days, interesting compounds are being developed, directed especially against homeostatic chemokine receptors.

Keywords::

• antagonist
• chemokine
• homing
• lymphoma
• metastasis

Acknowledgements

This work was supported by the Italian Association for Cancer Research (AIRC), the Associazione Italiana contro le Leucemia, Linfomi e Mieloma (AIL)-Sezione Paolo Belli, and Roche Italia.