Expression of TLR9 within human glioblastoma

Immunostimulating oligonucleotides containing CpG motifs (CpG-ODN) have shown promising antitumor activity in preclinical glioma models. CpG motifs are specifically recognized by the Toll-like receptor 9 (TLR9), mainly expressed in plasmacytoid dendritic cells (pDCs) and B cells. Expression of TLR9 within human glioma samples has not been investigated. As CpG-ODN is currently under clinical trials in glioma patients, we investigated whether TLR9 is expressed at the RNA levels in a series of 37 human glioblastomas (GBM) by quantitative PCR. TLR9 expression was detected at variable levels, which might suggest that some patients are more likely to benefit from treatment with CpG-ODN than others. No significant relationships between TLR9 expression and age, sex, tumor location, lymphocytes infiltration, oligodendroglial components or survival were found. TLR9 is unlikely to be expressed by tumor cells as no TLR9 expression was detected in pure human GBM xenografts. Immunocytochemistry studies showed TLR9 expression in some macrophages/microglial cells. The expression of TLR9 within human GBM strengthens the rationale for the utilization of CpG-ODN in this disease.