Cancer Immunology, Immunotherapy

, Volume 56, Issue 9, pp 1323-1334

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

  • Emma di CarloAffiliated withDipartimento di Oncologia e Neuroscienze, Sezione di Patologia Chirurgica, and Ce.S.I. Aging Research Center, Fondazione Universitaria “G. d’Annunzio”
  • , Daniela de ToteroAffiliated withImmunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro
  • , Tiziana PiazzaAffiliated withImmunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro
  • , Marina FabbiAffiliated withImmunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro
  • , Silvano FerriniAffiliated withImmunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro Email author 

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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.


Interleukin-21 Immune-regulation Lymphoid neoplasia Tumor immunotherapy