Interleukin-21 and cancer therapy

Ian D. Davis, Kresten Skak, Naomi Hunder, Mark J. Smyth, Pallavur V. Sivakumar

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review


Interleukin-21 (IL-21) is a pleiotropic cytokine structurally similar to IL-2 and IL-15 but with important distinctions in its biological properties. IL-21 is mainly secreted by activated CD4+ T cells, NKT cells, and follicular T helper (Tfh) cells. The IL-21 receptor is expressed physiologically on lymphoid tissues and peripheral blood mononuclear cells, although expression can be acquired by epithelial, synovial, or transformed cells. The effects of IL-21 signaling include enhancement of adaptive T cell immunity, promotion of antibody production, activation of innate immune responses through NK cells, opposition to immune downmodulation mediated through regulatory T cells, and effects in autoimmunity. IL-21 also has important roles in development of Th17 and Tfh cells. In preclinical models and clinical trials in humans, IL-21 has been shown to mediate anticancer effects either as a single agent or in combination with other strategies such as monoclonal antibodies or tyrosine kinase inhibitors. The biology of IL-21 suggests that it could also be usefully combined with active vaccination, adoptive immunotherapy, or cytotoxic chemotherapy. IL-21 continues to undergo clinical development for a variety of cancer indications.

Original languageEnglish
Title of host publicationTargeted Cancer Immune Therapy
Number of pages17
ISBN (Print)9781441901699
Publication statusPublished - 2009
Externally publishedYes

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