Interleukin 21 – its potential role in the therapy of B-cell lymphomas

Abstract

Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21’s ability to activate cytolytic activities by NK-cells and CD4⁺/CD8⁺ T-cells. In this review, we provide an overview of IL-21’s effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

Keywords:

• Interleukin-21
• B-cell lymphoma therapy
• NK-cell mediated cytotoxicity
• STAT3
• cMyc

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1201568.2016.1201568

Funding information

I.S.L. is supported by the Sylvester Comprehensive Cancer Center and by the Dwoskin, Recio and Anthony Rizzo Family Foundations.