A balance of interleukin-12 and -23 in cancer

• Host IL-12 suppresses tumors, whereas host IL-23 promotes tumors.
• Exogenous IL-23 suppresses established tumor growth.
• IL-23 production by APCs is specifically regulated.
• Blockade of IL-23 may be clinically safer than blockade of both IL-12 and IL-23.

Interleukin (IL)-12 and IL-23 share the IL-12p40 molecule. IL-12 promotes T helper (Th)1 immunity and IL-23 promotes Th17 immunity, and it has recently become apparent that the balance between IL-12 and IL-23 is important in carcinogenesis. A series of studies demonstrated that, where tumor initiation, growth, and metastasis are concerned, IL-12 may act independently of interferon (IFN)-γ, and IL-23 independently of IL-17A. This review explores the activity of IL-23 in carcinogenesis. In the context of the tumor-inhibitory effects of IL-12, and tumor-promoting effects of IL-23, we discuss the use of anti-IL-12p/23 monoclonal antibodies (mAbs) in autoimmune inflammatory disorders and the alternative specific neutralization of IL-23.