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

Shruti Bhatt, Kristopher A. Sarosiek, Izidore Lossos

Research output: Contribution to journalReview article

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)17-29
Number of pages13
JournalLeukemia and Lymphoma
Volume58
Issue number1
DOIs
StatePublished - Jan 2 2017

Fingerprint

B-Cell Lymphoma
Non-Hodgkin's Lymphoma
B-Lymphocytes
Hematologic Neoplasms
Therapeutics
Lymphoma
Neoplasms
Burkitt Lymphoma
interleukin-21
Myeloid Cells
Multiple Myeloma
Hodgkin Disease
Natural Killer Cells
Interleukin-2
Signal Transduction
Cell Death
Clinical Trials
Lymphocytes
Apoptosis
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Interleukin 21 – its potential role in the therapy of B-cell lymphomas. / Bhatt, Shruti; Sarosiek, Kristopher A.; Lossos, Izidore.

In: Leukemia and Lymphoma, Vol. 58, No. 1, 02.01.2017, p. 17-29.

Research output: Contribution to journalReview article

Bhatt, Shruti ; Sarosiek, Kristopher A. ; Lossos, Izidore. / Interleukin 21 – its potential role in the therapy of B-cell lymphomas. In: Leukemia and Lymphoma. 2017 ; Vol. 58, No. 1. pp. 17-29.
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