An immune regulatory cytokine receptor and glioblastoma multiforme: an unexpected link

Abstract

Human high-grade gliomas (HGG) are one of the most devastating human malignancies. They are rapidly progressing heterogenous tumors for which no curable treatment is available. Although these tumors are believed to be of glial cell origin, known tumor-specific markers do not characterize them. The specific environmental conditions that cause or promote the development of HGG are not known. The pathomechanism of HGG is yet to be revealed, although more specific genetic alterations are assigned to HGG. Recently, we have found that HGG overexpress a receptor for an immune regulatory cytokine, interleukin-13 (IL-13). In fact, it appears that all patients with glioblastoma multiforme may possess this receptor. IL-13 is an antiinflammatory cytokine with many overlapping functions to its homologue, IL-4. There is a high degree of specificity of the overexpression of the IL-13 receptor in HGG. This receptor is not only quantitatively but also qualitatively different from the only known functional signaling receptor for IL-13 of normal tissue. It is not shared with IL-4. The more restrictive receptor for IL-13 thus may represent a new factor specific for a disease as heterogenous as HGG.