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Title: Interleukin-21 signaling: functions in cancer and autoimmunity.
Austin Authors: Davis, Ian D;Skak, Kresten;Smyth, Mark J;Kristjansen, Paul E G;Miller, Dennis M;Sivakumar, Pallavur V
Affiliation: Ludwig-Austin Joint Medical Oncology Unit, Austin Health, Melbourne, Australia
Issue Date: 1-Dec-2007
Publication information: Clinical Cancer Research; 13(23): 6926-32
Abstract: 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-21Ralpha; 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.
Gov't Doc #: 18056166
DOI: 10.1158/1078-0432.CCR-07-1238
Journal: Clinical Cancer Research
Type: Journal Article
Subjects: Animals
Interleukins.immunology.metabolism.therapeutic use
Receptors, Interleukin-21.immunology.metabolism
Signal Transduction
Appears in Collections:Journal articles

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