Originally published as JCO Early Release 10.1200/JCO.2008.21.3579 on August 31 2009

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Interleukin-12 Receptor β2: From Cytokine Receptor to Gatekeeper Gene in Human B-Cell Malignancies

From the Laboratory of Oncology, Department of Experimental and Laboratory Medicine; and Associazione Italiana per la Ricerca sul Cancro Tumor Immunology Unit, Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genoa, Italy

Corresponding author: Vito Pistoia, MD, Laboratory of Oncology, G. Gaslini Institute, Largo G. Gaslini 5, 16147 Genova, Italy; e-mail: vitopistoia{at}ospedale-gaslini.ge.it.

Interleukin (IL) -12 is a cytokine that has been extensively characterized for its immunoregulatory activities. IL-12 binds to a heterodimeric receptor composed of the β1 and β2 chains. In this review article, we discuss recent findings on the expression and function of IL-12 receptor (IL-12R) in malignant B cells frozen at various stages of differentiation and in their normal counterparts. These studies, together with others performed in Il12rb2 knockout mice, have established the concept that the IL-12Rβ2 gene is a gatekeeper from cancer. We will delineate three paradigms reflecting the differential expression of IL-12Rβ2 in different groups of malignant B cells and discuss the therapeutic perspectives stemming from these studies.

Supported by Grant Nos. 1429 (V.P.) and 4014 (I.A.) from Associazione Italiana per la Ricerca sul Cancro, Milano, Italy; and by grants from Ricerca Finalizzata Ministero della Salute 2006 – Programma Integrato Oncologia "Nuovi approcci diagnostici come base molecolare per lo sviluppo di terapie innovative nella cura delle neoplasie ematologiche" (V.P.) and Fondazione Wilma e Maria Querci (V. P.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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