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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||URI:||http://ahro.austin.org.au/austinjspui/handle/1/10475||DOI:||10.1158/1078-0432.CCR-07-1238||Journal:||Clinical Cancer Research||URL:||https://pubmed.ncbi.nlm.nih.gov/18056166||Type:||Journal Article||Subjects:||Animals
|Appears in Collections:||Journal articles|
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