Regeneration and tolerance factor: a novel mediator of glioblastoma-associated immunosuppression.
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.
Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. patrick.roth@uni-tuebingen.de
Patrick
P
Roth
Steffen
S
Aulwurm
Isabella
I
Gekel
Dagmar
D
Beier
Roxanne G
RG
Sperry
Michel
M
Mittelbronn
Richard
R
Meyermann
Kenneth D
KD
Beaman
Michael
M
Weller
Jörg
J
Wischhusen
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014183:Transplantation, Heterologous; D006180:Proton-Translocating ATPases
D012333:RNA, Messenger; D013491:Suppressor Factors, Immunologic; C525845:ATP6V0A2 protein, human; D006180:Proton-Translocating ATPases