di Carlo Emma, de Totero Daniela, Piazza Tiziana, Fabbi Marina, Ferrini Silvano
Dipartimento di Oncologia e Neuroscienze, Sezione di Patologia Chirurgica, Ce.S.I. Aging Research Center, Fondazione Universitaria G. d'Annunzio, Chieti, Italy.
Cancer Immunol Immunother. 2007 Sep;56(9):1323-34. doi: 10.1007/s00262-007-0326-z. Epub 2007 Apr 20.
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.
白细胞介素-21（IL-21）是白细胞介素-2细胞因子家族中最近发现的成员，由于其参与自身免疫实验模型、下调IgE产生的能力以及抗肿瘤特性，成为一个具有吸引力的研究对象。它在癌症免疫治疗方面的价值源于其生理免疫增强功能。这些功能包括调节T细胞、B细胞和自然杀伤（NK）细胞的增殖、存活、分化及效应功能。IL-21的功能活动部分重叠于IL-2。这两种细胞因子具有相似的结构特征，并利用共同的γ链受体及其下游信号通路。除了对正常淋巴细胞的作用外，IL-21是骨髓瘤和急性T细胞白血病细胞的体外生长因子，而它可诱导慢性淋巴细胞白血病（B-CLL）细胞凋亡。这些发现表明IL-21/IL-21R系统在不同的淋巴样肿瘤中发挥相反的作用，并提示其可用于B-CLL治疗。由于调节性T（Treg）细胞免疫抑制功能的发育特别需要IL-2而非IL-21，IL-21可能是癌症免疫治疗的一种新工具。事实上，通过激活针对肿瘤细胞的特异性或先天性免疫反应，它在多种小鼠实验性肿瘤模型中是一种强大的抗肿瘤剂。I期临床研究的初步数据表明，使用IL-21是可行的，可能会产生免疫增强效果。
