Insights into the role of IL-32 in cancer

Interleukin 32 (IL-32) is a proinflammatory cytokine involved in the development of several diseases, including cancer. IL-32 is a rather peculiar cytokine because its protein structure does not show resemblance with any of the known cytokines, and an IL-32 receptor to facilitate extracellular signaling has not yet been identified. Thus far, 9 isoforms of IL-32 have been described, all of which show differences in terms of effects and in potency to elicit a specific effect. Since the first report of IL-32 in 2005, there is increasing evidence that IL-32 plays an important role in the pathophysiology of both hematologic malignancies and solid tumors. Some IL-32 isoforms have been linked to disease outcome and were shown to positively influence tumor development and progression in various different malignancies, including gastric, breast and lung cancers. However, there are other reports suggesting a tumor suppressive role for some of IL-32 as well. For example, IL-32 gamma and IL-32 beta expression is associated with increased cancer cell death in colon cancer and melanoma, whereas expression of these isoforms is associated with increased invasion and migration in breast cancer cells. Furthermore, IL-32 isoforms alpha, beta and gamma also play an important role in regulating the anti-tumor immune response, thus also influencing tumor progression. In this review, we provide an overview of the role of IL-32 and its different isoforms in carcinogenesis, invasion and metastasis, angiogenesis and regulation of the anti-tumor immune response.