Role of IL-21 in immune-regulation and tumor immunotherapy.
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.
di Carlo
Emma
E
Dipartimento di Oncologia e Neuroscienze, Sezione di Patologia Chirurgica, Ce.S.I. Aging Research Center, Fondazione Universitaria G. d'Annunzio, Chieti, Italy. edicarlo@unich.it
de Totero
Daniela
D
Piazza
Tiziana
T
Fabbi
Marina
M
Ferrini
Silvano
S
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015551:Autoimmunity; D006801:Humans; D007167:Immunotherapy; D007378:Interleukins / Q000502:physiology* / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D000098546:Interleukin-21
D000970:Antineoplastic Agents; D007378:Interleukins; D000098546:Interleukin-21