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Role of IL-21 in immune-regulation and tumor immunotherapy

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Abstract

IL-21, the most recently discovered member of the IL-2 cytokine family, is an attractive subject for research due to its involvement in experimental models of autoimmunity, its ability to down-regulate IgE production, and its anti-tumor properties. Its interest for cancer immunotherapy stems from its physiological immune-enhancing functions. These include regulation of T, B and NK cell proliferation, survival, differentiation, and effector functions. IL-21’s functional activities partially overlap those of IL-2. Both cytokines display similar structural features and use the common γ-chain receptor and its downstream signaling pathways. Besides its activities on normal lymphoid cells, IL-21 is an in vitro growth factor for myeloma and acute-T cell leukemia cells, whereas it induces the apoptosis of B-CLL (chronic lymphocytic leukemia) cells. These findings indicate that the IL-21/IL-21R system exerts opposite functions in different lymphoid neoplasias, and suggest its employment in B-CLL therapy. Since IL-2, but not IL-21, is specifically required for the development of regulatory T (Treg) cell immune-suppressive functions, IL-21 may be a new tool for cancer immunotherapy. It is, in fact, a powerful anti-tumor agent in a variety of murine experimental tumor models through its activation of specific or innate immune responses against neoplastic cells. The preliminary data from phase-I clinical studies suggest that the use of IL-21 is feasible and may result in immune-enhancing effects.

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Acknowledgment

T. Piazza is supported by a fellowship awarded by FIRC (Fondazione Italiana per la Ricerca sul Cancro). Our work is supported by grants awarded by AIRC (Associazione Italiana per la Ricerca sul Cancro) and Italian Ministry of Health. We thank Prof. J. Illife for revising the manuscript.

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Authors and Affiliations

  1. Dipartimento di Oncologia e Neuroscienze, Sezione di Patologia Chirurgica, and Ce.S.I. Aging Research Center, Fondazione Universitaria “G. d’Annunzio”, Chieti, Italy

    Emma di Carlo

  2. Immunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro, C/o Centro di Biotecnologie Avanzate, 16132, Genoa, Italy

    Daniela de Totero, Tiziana Piazza, Marina Fabbi & Silvano Ferrini

Authors
  1. Emma di Carlo
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  2. Daniela de Totero
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  3. Tiziana Piazza
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  4. Marina Fabbi
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  5. Silvano Ferrini
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Corresponding author

Correspondence to Silvano Ferrini.

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di Carlo, E., de Totero, D., Piazza, T. et al. Role of IL-21 in immune-regulation and tumor immunotherapy. Cancer Immunol Immunother 56, 1323–1334 (2007). https://doi.org/10.1007/s00262-007-0326-z

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  • DOI: https://doi.org/10.1007/s00262-007-0326-z

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