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Regeneration and Tolerance Factor: A Novel Mediator of Glioblastoma-Associated Immunosuppression

¹ Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, and ² Institute for Brain Research, University of Tübingen, Medical School, Tübingen, Germany and ³ Clinical Immunology Laboratory, Department of Microbiology/Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois

Requests for reprints: Patrick Roth, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. Phone: 49-7071-2981960; Fax: 49-7071-295742; E-mail: patrick.roth{at}uni-tuebingen.de.

Regeneration and tolerance factor (RTF) was originally identified in placenta where it is thought to be essential for fetal allograft survival. Here we report that RTF mRNA and protein are also expressed in human glioma cells in vitro and in vivo. Suppression of RTF expression by RNA interference promotes the lysis of glioma cells by natural killer (NK) and T cells in vitro. Moreover, RTF-depleted glioma cells are less tumorigenic than control cells in nude mice in vivo. Depletion of NK cells in these animals abolished this effect. RTF is thus a novel aberrantly expressed molecule which confers immune privilege to human malignant gliomas. (Cancer Res 2006; 66(7): 3852-8)

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