title: 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.
authors.affiliation: a Dana-Farber Cancer Institute/Harvard Medical School , Boston , MA , USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: a Dana-Farber Cancer Institute/Harvard Medical School , Boston , MA , USA.
authors.forename: Kristopher A
authors.initials: KA
authors.lastname: Sarosiek
authors.affiliation: b Department of Molecular and Cellular Pharmacology , University of Miami Miller School of Medicine , Miami , FL , USA.|c Department of Medicine, Division of Hematology-Oncology , Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami , FL , USA.
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D056747:Immunomodulation / Q000187:drug effects; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D000098546:Interleukin-21
chemical_list: D007155:Immunologic Factors; D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21
keywords: B-cell lymphoma therapy; Interleukin-21; NK-cell mediated cytotoxicity; STAT3; cMyc