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

• Published in: Cancer Immunology, Immunotherapy Vol. 56; no. 9; pp. 1323 - 1334
• Main Authors: di Carlo, Emma, de Totero, Daniela, Piazza, Tiziana, Fabbi, Marina, Ferrini, Silvano
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.09.2007; Springer-Verlag
• Subjects: Animal models; Antigens; Antineoplastic Agents - therapeutic use; Apoptosis; Autoimmunity; Cancer; Cancer immunotherapy; Cell differentiation; Cell growth; Cell proliferation; Cell survival; Chronic lymphocytic leukemia; Cytokines; Humans; Immunoglobulin E; Immunotherapy; Innate immunity; Interleukin 2; Interleukin 21; Interleukins - physiology; Interleukins - therapeutic use; Kinases; Leukemia; Ligands; Lymphocytes; Lymphocytes T; Lymphoid cells; Myeloma; Natural killer cells; Neoplasms - drug therapy; Review; Signal transduction; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-007-0326-z

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 gamma-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.