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 language | English (US) |
|---|---|
| Pages (from-to) | 17-29 |
| Number of pages | 13 |
| Journal | Leukemia and Lymphoma |
| Volume | 58 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2 2017 |
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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 journal › Review article
}
TY - JOUR
T1 - Interleukin 21 – its potential role in the therapy of B-cell lymphomas
AU - Bhatt, Shruti
AU - Sarosiek, Kristopher A.
AU - Lossos, Izidore
PY - 2017/1/2
Y1 - 2017/1/2
N2 - 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.
AB - 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.
KW - B-cell lymphoma therapy
KW - cMyc
KW - Interleukin-21
KW - NK-cell mediated cytotoxicity
KW - STAT3
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UR - http://www.scopus.com/inward/citedby.url?scp=84994513754&partnerID=8YFLogxK
U2 - 10.1080/10428194.2016.1201568
DO - 10.1080/10428194.2016.1201568
M3 - Review article
C2 - 27405876
AN - SCOPUS:84994513754
VL - 58
SP - 17
EP - 29
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 1
ER -