Malignant glioma cells counteract antitumor immune responses through expression of lectin-like transcript-1.
Glioblastoma, one of the most lethal tumors, is paradigmatic for tumor-associated immunosuppression. Lectin-like transcript-1 (LLT1) is a newly identified ligand for the inhibitory natural killer (NK) cell receptor CD161. Here, we report that glioma cells express LLT1 mRNA and protein in vitro and in vivo, whereas expression levels in normal brain are low. LLT1 expression in human gliomas increases with the WHO grade of malignancy. We further show that transforming growth factor-beta (TGF-beta) up-regulates the expression of LLT1 in glioma cells. Small interfering RNA (siRNA)-mediated down-regulation of LLT1 in LNT-229 and LN-428 cells promotes their lysis by NK cells. Thus, LLT1 acts as a mediator of immune escape and contributes to the immunosuppressive properties of glioma cells.
Roth
Patrick
P
Laboratory of Molecular Neuro-Oncology, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. patrick.roth@uni-tuebingen.de
Mittelbronn
Michel
M
Wick
Wolfgang
W
Meyermann
Richard
R
Tatagiba
Marcos
M
Weller
Michael
M
D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005910:Glioma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000954:Antigens, Surface; C400041:CLEC2D protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta