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Targeted Cancer Immune Therapy pp 43–59Cite as

Interleukin-21 and Cancer Therapy

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Abstract

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.

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Acknowledgments

IDD is supported in part by a Victorian Cancer Agency Clinician Researcher Fellowship and is an Australian National Health and Medical Research Council Honorary Practitioner Fellow. MJS is supported by a NH&MRC Senior Principal Research Fellowship and Program Grant.

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Authors and Affiliations

  1. Ludwig-Austin Joint Medical Oncology Unit, Austin Health, Melbourne, Australia

    Ian D. Davis

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  1. Ian D. Davis
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  2. Kresten Skak
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  3. Naomi Hunder
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  4. Mark J. Smyth
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  5. Pallavur V. Sivakumar
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Correspondence to Ian D. Davis .

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  1. Sidney Kimmel Cancer Center, Altman Row 10835, San Diego, 92121, U.S.A.

    Joseph Lustgarten

  2. Health Sciences Center, Louisiana State University, Bolivar Street 533, New Orleans, 70112, U.S.A.

    Yan Cui

  3. School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, 70803, U.S.A.

    Shulin Li

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Davis, I.D., Skak, K., Hunder, N., Smyth, M.J., Sivakumar, P.V. (2009). Interleukin-21 and Cancer Therapy. In: Lustgarten, J., Cui, Y., Li, S. (eds) Targeted Cancer Immune Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0170-5_3

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