Immune escape of malignant gliomas – regulation of NKG2D ligands by TGF-beta and matrix metalloproteinases

Gliomas are the most frequent primary brain tumors with an incidence of up to 5 per 100.000. For tumorigenesis escape from immunosurveillance is essential. A major mediator of anti-tumor immunity is the lectin-like NKG2D immunoreceptor which is expressed by natural killer (NK) and CD8+ alpha/beta and gamma/delta T cells. NKG2D ligands (NKG2DL) are absent from somatic cells (with the exception of the intestinal epithelium), but are induced upon transformation or infection, leading to NK or T cell-mediated lysis of NKG2DL-expressing cells. Gliomas shape their microenvironment by secreting proteolytically active en…