Interleukin-21 signaling: Functions in cancer and autoimmunity

被引:73
作者
Davis, Ian D.
Skak, Kresten
Smyth, Mark J.
Kristjansen, Paul E. G.
Miller, Dennis M.
Sivakumar, Pallavur V.
机构
[1] Ludwig Austin Med Oncol Unit, Melbourne, Vic 3084, Australia
[2] Peter MacCallum Canc Ctr, Melbourne, Vic 3084, Australia
[3] Novo Nordisk, Copenhagen, Denmark
[4] ZymoGen, Seattle, WA USA
关键词
D O I
10.1158/1078-0432.CCR-07-1238
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15, yet possesses several biological properties distinct from these cytokines. IL-21 is produced mainly by activated CD4(+) T cells and natural killer T cells and mediates its activity by binding to the IL-21 receptor (IL-21R), consisting of an IL-21 - specific alpha chain (IL-21R alpha; JAK/STAT) that heterodimerizes with the common gamma chain (CD132). Intracellular signaling occurs through the Janus-activated kinase/signal transducer and activator of transcription pathways. Physiologic expression of IL-21R is restricted to lymphoid tissues and peripheral blood mononuclear cells; however, other tissues such as epithelium, synovium, or transformed cells can acquire expression of both components of IL-21R heterodimer. IL-21 has complex activities on a wide variety of cell types, leading to enhancement of adaptive T-cell immunity, antibody production, activation of natural killer cell subtypes, and opposition to suppressive effects mediated by regulatory T cells. Functionally, these activities promote immune responses and point to a physiologic role of IL-21 in autoimmunity and immune enhancement. Therapeutic manipulation of IL-21 activity may allow improved immunotherapy for cancer as well as insights into autoimmune disease. Recently conducted phase 1 trials in metastatic melanoma and renal cell carcinoma have shown that recombinant IL-21 has a favorable safety profile and support its continued investigation as a potential anticancer drug.
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收藏
页码:6926 / 6932
页数:7
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